PDBsum entry 1ir3

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Complex (transferase/substrate) PDB id
Protein chain
303 a.a. *
_MG ×2
Waters ×202
* Residue conservation analysis
PDB id:
Name: Complex (transferase/substrate)
Title: Phosphorylated insulin receptor tyrosine kinase in complex with peptide substrate and atp analog
Structure: Insulin receptor. Chain: a. Fragment: tyrosine kinase domain. Engineered: yes. Mutation: yes. Peptide substrate. Chain: b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Biol. unit: Tetramer (from PDB file)
1.90Å     R-factor:   0.194     R-free:   0.226
Authors: S.R.Hubbard
Key ref:
S.R.Hubbard (1997). Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog. EMBO J, 16, 5572-5581. PubMed id: 9312016 DOI: 10.1093/emboj/16.18.5572
22-Sep-97     Release date:   07-Jan-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P06213  (INSR_HUMAN) -  Insulin receptor
1382 a.a.
303 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Bound ligand (Het Group name = TYR)
matches with 70.00% similarity
Bound ligand (Het Group name = ANP)
matches with 81.00% similarity
+ [protein]-L-tyrosine phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     transmembrane receptor protein tyrosine kinase signaling pathway   2 terms 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     5 terms  


DOI no: 10.1093/emboj/16.18.5572 EMBO J 16:5572-5581 (1997)
PubMed id: 9312016  
Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog.
The crystal structure of the phosphorylated, activated form of the insulin receptor tyrosine kinase in complex with a peptide substrate and an ATP analog has been determined at 1.9 A resolution. The activation loop (A-loop) of the kinase undergoes a major conformational change upon autophosphorylation of Tyr1158, Tyr1162 and Tyr1163 within the loop, resulting in unrestricted access of ATP and protein substrates to the kinase active site. Phosphorylated Tyr1163 (pTyr1163) is the key phosphotyrosine in stabilizing the conformation of the tris-phosphorylated A-loop, whereas pTyr1158 is completely solvent-exposed, suggesting an availability for interaction with downstream signaling proteins. The YMXM-containing peptide substrate binds as a short anti-parallel beta-strand to the C-terminal end of the A-loop, with the methionine side chains occupying two hydrophobic pockets on the C-terminal lobe of the kinase. The structure thus reveals the molecular basis for insulin receptor activation via autophosphorylation, and provides insights into tyrosine kinase substrate specificity and the mechanism of phosphotransfer.
  Selected figure(s)  
Figure 1.
Figure 1 Electron density map of the active site of IRK3P. Stereo view of a 2F[o] -F[c] map computed at 1.9 Ć resolution and contoured at 1.2 . Superimposed is the refined atomic model. Carbon atoms are yellow, oxygen atoms red, nitrogen atoms blue, phosphate atoms purple, and sulfur atoms green. The red spheres represent water molecules and the white spheres represent Mg2+ ions. Figure prepared with SETOR (Evans, 1993).
Figure 2.
Figure 2 Overall view of IRK3P and comparison with IRK. (A) Ribbon diagram of the IRK3P structure. The -helices are shown in red, the -strands in blue, the nucleotide-binding loop in yellow, the catalytic loop in orange, the activation loop in green, AMP-PNP in black and the peptide substrate in pink. The termini are denoted by N and C. (B) Superposition of the C-terminal lobes of IRK and IRK3P. The backbone representation of IRK/IRK3P is colored orange/green, with the activation loop colored red/blue. The axis (black) and arrow (blue) specify the rotation required to align the N-terminal -sheet of IRK with that of IRK3P. (C) Superposition of the -sheets in the N-terminal lobes of IRK and IRK3P. The backbone representation and carbon atoms of IRK/IRK3P are colored orange/green, oxygen atoms are red and nitrogen atoms are blue. (A) and (C) prepared with RIBBONS (Carson, 1991), (B) with GRASP (Nicholls et al., 1991).
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1997, 16, 5572-5581) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22504184 C.C.Smith, Q.Wang, C.S.Chin, S.Salerno, L.E.Damon, M.J.Levis, A.E.Perl, K.J.Travers, S.Wang, J.P.Hunt, P.P.Zarrinkar, E.E.Schadt, A.Kasarskis, J.Kuriyan, and N.P.Shah (2012).
Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia.
  Nature, 485, 260-263.  
22820988 R.M.Bandaranayake, D.Ungureanu, Y.Shan, D.E.Shaw, O.Silvennoinen, and S.R.Hubbard (2012).
Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F.
  Nat Struct Mol Biol, 19, 754-759.
PDB codes: 4fvp 4fvq 4fvr
21205204 G.Ghosh, and J.A.Adams (2011).
Phosphorylation mechanism and structure of serine-arginine protein kinases.
  FEBS J, 278, 587-597.  
21056590 J.Biarc, R.J.Chalkley, A.L.Burlingame, and R.A.Bradshaw (2011).
Receptor tyrosine kinase signaling - a proteomic perspective.
  Adv Enzyme Regul, 51, 293-305.  
21515061 M.Okamoto, H.Kojima, N.Saito, T.Okabe, Y.Masuda, T.Furuya, and T.Nagano (2011).
Virtual screening and further development of novel ALK inhibitors.
  Bioorg Med Chem, 19, 3086-3095.  
21474065 N.Jura, X.Zhang, N.F.Endres, M.A.Seeliger, T.Schindler, and J.Kuriyan (2011).
Catalytic control in the EGF receptor and its connection to general kinase regulatory mechanisms.
  Mol Cell, 42, 9.  
19774589 D.Lavogina, E.Enkvist, and A.Uri (2010).
Bisubstrate inhibitors of protein kinases: from principle to practical applications.
  ChemMedChem, 5, 23-34.  
20603078 E.Bergamin, P.T.Hallock, S.J.Burden, and S.R.Hubbard (2010).
The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization.
  Mol Cell, 39, 100-109.
PDB code: 3ml4
20352052 H.You, W.Zhang, M.K.Jones, G.N.Gobert, J.Mulvenna, G.Rees, M.Spanevello, D.Blair, M.Duke, K.Brehm, and D.P.McManus (2010).
Cloning and characterisation of Schistosoma japonicum insulin receptors.
  PLoS One, 5, e9868.  
20121196 K.P.Ravindranathan, V.Mandiyan, A.R.Ekkati, J.H.Bae, J.Schlessinger, and W.L.Jorgensen (2010).
Discovery of novel fibroblast growth factor receptor 1 kinase inhibitors by structure-based virtual screening.
  J Med Chem, 53, 1662-1672.
PDB code: 3js2
20637424 Y.W.Ng, D.Raghunathan, P.M.Chan, Y.Baskaran, D.J.Smith, C.H.Lee, C.Verma, and E.Manser (2010).
Why an A-loop phospho-mimetic fails to activate PAK1: understanding an inaccessible kinase state by molecular dynamics simulations.
  Structure, 18, 879-890.  
20638297 Z.Cheng, Y.Tseng, and M.F.White (2010).
Insulin signaling meets mitochondria in metabolism.
  Trends Endocrinol Metab, 21, 589-598.  
19334696 B.Zhou, and C.F.Wong (2009).
A computational study of the phosphorylation mechanism of the insulin receptor tyrosine kinase.
  J Phys Chem A, 113, 5144-5150.  
19274663 C.W.Ward, and M.C.Lawrence (2009).
Ligand-induced activation of the insulin receptor: a multi-step process involving structural changes in both the ligand and the receptor.
  Bioessays, 31, 422-434.  
19224897 E.D.Lew, C.M.Furdui, K.S.Anderson, and J.Schlessinger (2009).
The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutations.
  Sci Signal, 2, ra6.  
19642985 H.J.Tsai, and S.Y.Chou (2009).
A novel hydroxyfuroic acid compound as an insulin receptor activator structure and activity relationship of a prenylindole moiety to insulin receptor activation.
  J Biomed Sci, 16, 68.  
19665973 J.H.Bae, E.D.Lew, S.Yuzawa, F.Tomé, I.Lax, and J.Schlessinger (2009).
The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site.
  Cell, 138, 514-524.
PDB codes: 3gqi 3gql
19103250 J.Papaconstantinou (2009).
Insulin/IGF-1 and ROS signaling pathway cross-talk in aging and longevity determination.
  Mol Cell Endocrinol, 299, 89.  
19260709 K.E.Muratore, M.A.Seeliger, Z.Wang, D.Fomina, J.Neiswinger, J.J.Havranek, D.Baker, J.Kuriyan, and P.A.Cole (2009).
Comparative analysis of mutant tyrosine kinase chemical rescue.
  Biochemistry, 48, 3378-3386.
PDB code: 3geq
  19956424 M.Yin, X.Guan, Z.Liao, and Q.Wei (2009).
Insulin-like growth factor-1 receptor-targeted therapy for non-small cell lung cancer: a mini review.
  Am J Transl Res, 1, 101-114.  
18623061 N.K.Banavali, and B.Roux (2009).
Flexibility and charge asymmetry in the activation loop of Src tyrosine kinases.
  Proteins, 74, 378-389.  
19110212 R.Bargal, V.Cormier-Daire, Z.Ben-Neriah, M.Le Merrer, J.Sosna, J.Melki, D.H.Zangen, S.F.Smithson, Z.Borochowitz, R.Belostotsky, and A.Raas-Rothschild (2009).
Mutations in DDR2 gene cause SMED with short limbs and abnormal calcifications.
  Am J Hum Genet, 84, 80-84.  
19150426 R.Barouch-Bentov, J.Che, C.C.Lee, Y.Yang, A.Herman, Y.Jia, A.Velentza, J.Watson, L.Sternberg, S.Kim, N.Ziaee, A.Miller, C.Jackson, M.Fujimoto, M.Young, S.Batalov, Y.Liu, M.Warmuth, T.Wiltshire, M.P.Cooke, and K.Sauer (2009).
A conserved salt bridge in the G loop of multiple protein kinases is important for catalysis and for in vivo Lyn function.
  Mol Cell, 33, 43-52.  
18761339 R.Bose, and X.Zhang (2009).
The ErbB kinase domain: structural perspectives into kinase activation and inhibition.
  Exp Cell Res, 315, 649-658.  
19290922 R.E.Joseph, and A.H.Andreotti (2009).
Conformational snapshots of Tec kinases during signaling.
  Immunol Rev, 228, 74-92.  
19523959 R.E.Joseph, A.Severin, L.Min, D.B.Fulton, and A.H.Andreotti (2009).
SH2-dependent autophosphorylation within the Tec family kinase Itk.
  J Mol Biol, 391, 164-177.  
19651772 R.Scholz, M.Suter, T.Weimann, C.Polge, P.V.Konarev, R.F.Thali, R.D.Tuerk, B.Viollet, T.Wallimann, U.Schlattner, and D.Neumann (2009).
Homo-oligomerization and activation of AMP-activated protein kinase are mediated by the kinase domain alphaG-helix.
  J Biol Chem, 284, 27425-27437.  
19497423 R.V.Rajala, and A.Rajala (2009).
Cytoskeletal components enhance the autophosphorylation of retinal insulin receptor.
  Chem Biol Interact, 180, 245-253.  
19289058 S.E.Telesco, and R.Radhakrishnan (2009).
Atomistic insights into regulatory mechanisms of the HER2 tyrosine kinase domain: a molecular dynamics study.
  Biophys J, 96, 2321-2334.  
19678838 T.L.Davis, J.R.Walker, A.Allali-Hassani, S.A.Parker, B.E.Turk, and S.Dhe-Paganon (2009).
Structural recognition of an optimized substrate for the ephrin family of receptor tyrosine kinases.
  FEBS J, 276, 4395-4404.
PDB codes: 3fxx 3fy2
19141286 X.Min, R.Akella, H.He, J.M.Humphreys, S.E.Tsutakawa, S.J.Lee, J.A.Tainer, M.H.Cobb, and E.J.Goldsmith (2009).
The structure of the MAP2K MEK6 reveals an autoinhibitory dimer.
  Structure, 17, 96.
PDB code: 3enm
19029291 Y.W.Tan, J.A.Hanson, and H.Yang (2009).
Direct Mg2+ Binding Activates Adenylate Kinase from Escherichia coli.
  J Biol Chem, 284, 3306-3313.  
19015641 Z.Tang, S.Jiang, R.Du, E.T.Petri, A.El-Telbany, P.S.Chan, T.Kijima, S.Dietrich, K.Matsui, M.Kobayashi, S.Sasada, N.Okamoto, H.Suzuki, K.Kawahara, T.Iwasaki, K.Nakagawa, I.Kawase, J.G.Christensen, T.Hirashima, B.Halmos, R.Salgia, T.J.Boggon, J.A.Kern, and P.C.Ma (2009).
Disruption of the EGFR E884-R958 ion pair conserved in the human kinome differentially alters signaling and inhibitor sensitivity.
  Oncogene, 28, 518-533.  
18579784 A.Torkamani, N.Kannan, S.S.Taylor, and N.J.Schork (2008).
Congenital disease SNPs target lineage specific structural elements in protein kinases.
  Proc Natl Acad Sci U S A, 105, 9011-9016.  
17971450 E.J.Kennedy, G.Ghosh, and L.Pillus (2008).
Identification of functionally distinct regions that mediate biological activity of the protein kinase a homolog Tpk2.
  J Biol Chem, 283, 1084-1093.  
18687871 E.Ozkirimli, S.S.Yadav, W.T.Miller, and C.B.Post (2008).
An electrostatic network and long-range regulation of Src kinases.
  Protein Sci, 17, 1871-1880.  
19060208 H.Chen, C.F.Xu, J.Ma, A.V.Eliseenkova, W.Li, P.M.Pollock, N.Pitteloud, W.T.Miller, T.A.Neubert, and M.Mohammadi (2008).
A crystallographic snapshot of tyrosine trans-phosphorylation in action.
  Proc Natl Acad Sci U S A, 105, 19660-19665.
PDB code: 3cly
18184589 J.Eswaran, A.Bernad, J.M.Ligos, B.Guinea, J.E.Debreczeni, F.Sobott, S.A.Parker, R.Najmanovich, B.E.Turk, and S.Knapp (2008).
Structure of the human protein kinase MPSK1 reveals an atypical activation loop architecture.
  Structure, 16, 115-124.  
18566589 J.Wu, W.Li, B.P.Craddock, K.W.Foreman, M.J.Mulvihill, Q.S.Ji, W.T.Miller, and S.R.Hubbard (2008).
Small-molecule inhibition and activation-loop trans-phosphorylation of the IGF1 receptor.
  EMBO J, 27, 1985-1994.
PDB code: 3d94
18278056 J.Wu, Y.D.Tseng, C.F.Xu, T.A.Neubert, M.F.White, and S.R.Hubbard (2008).
Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2.
  Nat Struct Mol Biol, 15, 251-258.
PDB codes: 3bu3 3bu5 3bu6
18841497 K.Kundrapu, L.Colenberg, and R.J.Duhé (2008).
Activation loop tyrosines allow the JAK2(V617F) mutant to attain hyperactivation.
  Cell Biochem Biophys, 52, 103-112.  
17849478 M.Abe, Y.Kuroda, M.Hirose, M.Kato, M.Murakami, Y.Watanabe, M.Nakano, and T.Handa (2008).
Inhibition of autophosphorylation of epidermal growth factor receptor by a small peptide not employing an ATP-competitive mechanism.
  Biopolymers, 89, 40-51.  
18767165 N.Katayama, M.Orita, T.Yamaguchi, H.Hisamichi, S.Kuromitsu, H.Kurihara, H.Sakashita, Y.Matsumoto, S.Fujita, and T.Niimi (2008).
Identification of a key element for hydrogen-bonding patterns between protein kinases and their inhibitors.
  Proteins, 73, 795-801.
PDB codes: 2z7l 2z8c
18324780 P.R.Sheth, J.L.Hays, L.A.Elferink, and S.J.Watowich (2008).
Biochemical basis for the functional switch that regulates hepatocyte growth factor receptor tyrosine kinase activation.
  Biochemistry, 47, 4028-4038.  
17710364 S.W.Zhang, Y.L.Zhang, Q.Pan, Y.M.Cheng, and K.C.Chou (2008).
Estimating residue evolutionary conservation by introducing von Neumann entropy and a novel gap-treating approach.
  Amino Acids, 35, 495-501.  
18319738 S.Y.Park, and S.E.Shoelson (2008).
When a domain is not a domain.
  Nat Struct Mol Biol, 15, 224-226.  
18215309 Z.I.Storozheva, A.T.Proshin, V.V.Sherstnev, T.P.Storozhevykh, Y.E.Senilova, N.A.Persiyantseva, V.G.Pinelis, N.A.Semenova, E.I.Zakharova, and I.A.Pomytkin (2008).
Dicholine salt of succinic acid, a neuronal insulin sensitizer, ameliorates cognitive deficits in rodent models of normal aging, chronic cerebral hypoperfusion, and beta-amyloid peptide-(25-35)-induced amnesia.
  BMC Pharmacol, 8, 1.  
17318838 A.Garza-Garcia, D.S.Patel, D.Gems, and P.C.Driscoll (2007).
RILM: a web-based resource to aid comparative and functional analysis of the insulin and IGF-1 receptor family.
  Hum Mutat, 28, 660-668.  
17185414 A.V.Galkin, J.S.Melnick, S.Kim, T.L.Hood, N.Li, L.Li, G.Xia, R.Steensma, G.Chopiuk, J.Jiang, Y.Wan, P.Ding, Y.Liu, F.Sun, P.G.Schultz, N.S.Gray, and M.Warmuth (2007).
Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK.
  Proc Natl Acad Sci U S A, 104, 270-275.  
17586502 B.P.Craddock, C.Cotter, and W.T.Miller (2007).
Autoinhibition of the insulin-like growth factor I receptor by the juxtamembrane region.
  FEBS Lett, 581, 3235-3240.  
17002595 C.J.Hupfeld, and J.M.Olefsky (2007).
Regulation of receptor tyrosine kinase signaling by GRKs and beta-arrestins.
  Annu Rev Physiol, 69, 561-577.  
17132625 C.Schalk-Hihi, H.C.Ma, G.T.Struble, S.Bayoumy, R.Williams, E.Devine, I.P.Petrounia, T.Mezzasalma, L.Zeng, C.Schubert, B.Grasberger, B.A.Springer, and I.C.Deckman (2007).
Protein engineering of the colony-stimulating factor-1 receptor kinase domain for structural studies.
  J Biol Chem, 282, 4085-4093.  
17574028 D.Lietha, X.Cai, D.F.Ceccarelli, Y.Li, M.D.Schaller, and M.J.Eck (2007).
Structural basis for the autoinhibition of focal adhesion kinase.
  Cell, 129, 1177-1187.
PDB codes: 2j0j 2j0k 2j0l 2j0m
18056630 E.D.Lew, J.H.Bae, E.Rohmann, B.Wollnik, and J.Schlessinger (2007).
Structural basis for reduced FGFR2 activity in LADD syndrome: Implications for FGFR autoinhibition and activation.
  Proc Natl Acad Sci U S A, 104, 19802-19807.
PDB code: 3b2t
17167796 G.M.Verkhivker (2007).
In silico profiling of tyrosine kinases binding specificity and drug resistance using Monte Carlo simulations with the ensembles of protein kinase crystal structures.
  Biopolymers, 85, 333-348.  
17173284 G.M.Verkhivker (2007).
Computational proteomics of biomolecular interactions in the sequence and structure space of the tyrosine kinome: deciphering the molecular basis of the kinase inhibitors selectivity.
  Proteins, 66, 912-929.  
17803937 H.Chen, J.Ma, W.Li, A.V.Eliseenkova, C.Xu, T.A.Neubert, W.T.Miller, and M.Mohammadi (2007).
A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinases.
  Mol Cell, 27, 717-730.
PDB codes: 2psq 2pvf 2pvy 2pwl 2py3 2pz5 2pzp 2pzr 2q0b
17585314 J.A.Ubersax, and J.E.Ferrell (2007).
Mechanisms of specificity in protein phosphorylation.
  Nat Rev Mol Cell Biol, 8, 530-541.  
17912359 J.D.Knight, B.Qian, D.Baker, and R.Kothary (2007).
Conservation, variability and the modeling of active protein kinases.
  PLoS ONE, 2, e982.  
17292838 J.Eswaran, W.H.Lee, J.E.Debreczeni, P.Filippakopoulos, A.Turnbull, O.Fedorov, S.W.Deacon, J.R.Peterson, and S.Knapp (2007).
Crystal Structures of the p21-activated kinases PAK4, PAK5, and PAK6 reveal catalytic domain plasticity of active group II PAKs.
  Structure, 15, 201-213.
PDB codes: 2bva 2c30 2cdz 2f57
17553792 K.Fulzele, D.J.DiGirolamo, Z.Liu, J.Xu, J.L.Messina, and T.L.Clemens (2007).
Disruption of the insulin-like growth factor type 1 receptor in osteoblasts enhances insulin signaling and action.
  J Biol Chem, 282, 25649-25658.  
17380483 N.K.Banavali, and B.Roux (2007).
Anatomy of a structural pathway for activation of the catalytic domain of Src kinase Hck.
  Proteins, 67, 1096-1112.  
17897671 R.E.Joseph, D.B.Fulton, and A.H.Andreotti (2007).
Mechanism and functional significance of Itk autophosphorylation.
  J Mol Biol, 373, 1281-1292.  
17159996 S.Dadke, S.Cotteret, S.C.Yip, Z.M.Jaffer, F.Haj, A.Ivanov, F.Rauscher, K.Shuai, T.Ng, B.G.Neel, and J.Chernoff (2007).
Regulation of protein tyrosine phosphatase 1B by sumoylation.
  Nat Cell Biol, 9, 80-85.  
17229728 T.Morita, A.Yamashita, I.Kashima, K.Ogata, S.Ishiura, and S.Ohno (2007).
Distant N- and C-terminal domains are required for intrinsic kinase activity of SMG-1, a critical component of nonsense-mediated mRNA decay.
  J Biol Chem, 282, 7799-7808.  
17919343 T.P.Storozhevykh, Y.E.Senilova, N.A.Persiyantseva, V.G.Pinelis, and I.A.Pomytkin (2007).
Mitochondrial respiratory chain is involved in insulin-stimulated hydrogen peroxide production and plays an integral role in insulin receptor autophosphorylation in neurons.
  BMC Neurosci, 8, 84.  
17322911 T.Pawson, and N.Warner (2007).
Oncogenic re-wiring of cellular signaling pathways.
  Oncogene, 26, 1268-1275.  
17030621 W.Xu, X.Yuan, K.Beebe, Z.Xiang, and L.Neckers (2007).
Loss of Hsp90 association up-regulates Src-dependent ErbB2 activity.
  Mol Cell Biol, 27, 220-228.  
17534481 X.Liang, D.J.Campopiano, and P.J.Sadler (2007).
Metals in membranes.
  Chem Soc Rev, 36, 968-992.  
16980311 A.M.Burza, I.Pekala, J.Sikora, P.Siedlecki, P.MaƂagocki, M.Bucholc, L.Koper, P.Zielenkiewicz, M.Dadlez, and G.Dobrowolska (2006).
Nicotiana tabacum osmotic stress-activated kinase is regulated by phosphorylation on Ser-154 and Ser-158 in the kinase activation loop.
  J Biol Chem, 281, 34299-34311.  
17095602 A.P.Kornev, N.M.Haste, S.S.Taylor, and L.F.Eyck (2006).
Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism.
  Proc Natl Acad Sci U S A, 103, 17783-17788.  
16628247 E.S.Groban, A.Narayanan, and M.P.Jacobson (2006).
Conformational changes in protein loops and helices induced by post-translational phosphorylation.
  PLoS Comput Biol, 2, e32.  
16945014 G.J.Zaman, M.M.van der Lee, J.J.Kok, R.L.Nelissen, and E.E.Loomans (2006).
Enzyme fragment complementation binding assay for p38alpha mitogen-activated protein kinase to study the binding kinetics of enzyme inhibitors.
  Assay Drug Dev Technol, 4, 411-420.  
16828554 H.Remaut, and G.Waksman (2006).
Protein-protein interaction through beta-strand addition.
  Trends Biochem Sci, 31, 436-444.  
16382158 K.B.Gagnon, R.England, and E.Delpire (2006).
Characterization of SPAK and OSR1, regulatory kinases of the Na-K-2Cl cotransporter.
  Mol Cell Biol, 26, 689-698.  
16707497 K.Y.Cheng, M.E.Noble, V.Skamnaki, N.R.Brown, E.D.Lowe, L.Kontogiannis, K.Shen, P.A.Cole, G.Siligardi, and L.N.Johnson (2006).
The role of the phospho-CDK2/cyclin A recruitment site in substrate recognition.
  J Biol Chem, 281, 23167-23179.
PDB codes: 2cch 2cci
17158707 M.A.Bogoyevitch, and B.Kobe (2006).
Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinases.
  Microbiol Mol Biol Rev, 70, 1061-1095.  
16402038 M.Abe, Y.Kuroda, M.Hirose, Y.Watanabe, M.Nakano, and T.Handa (2006).
Inhibition of autophosphorylation of epidermal growth factor receptor by small peptides in vitro.
  Br J Pharmacol, 147, 402-411.  
16640460 N.M.Levinson, O.Kuchment, K.Shen, M.A.Young, M.Koldobskiy, M.Karplus, P.A.Cole, and J.Kuriyan (2006).
A Src-like inactive conformation in the abl tyrosine kinase domain.
  PLoS Biol, 4, e144.
PDB codes: 2g1t 2g2f 2g2h 2g2i
17079130 P.Pellicena, and J.Kuriyan (2006).
Protein-protein interactions in the allosteric regulation of protein kinases.
  Curr Opin Struct Biol, 16, 702-709.  
17085043 R.Bose, M.A.Holbert, K.A.Pickin, and P.A.Cole (2006).
Protein tyrosine kinase-substrate interactions.
  Curr Opin Struct Biol, 16, 668-675.  
16286478 R.D.Meyer, M.Mohammadi, and N.Rahimi (2006).
A single amino acid substitution in the activation loop defines the decoy characteristic of VEGFR-1/FLT-1.
  J Biol Chem, 281, 867-875.  
16431914 R.D.Meyer, X.Qian, H.C.Guo, and N.Rahimi (2006).
Leucine motif-dependent tyrosine autophosphorylation of type III receptor tyrosine kinases.
  J Biol Chem, 281, 8620-8627.  
16788977 S.Kamath, and J.K.Buolamwini (2006).
Targeting EGFR and HER-2 receptor tyrosine kinases for cancer drug discovery and development.
  Med Res Rev, 26, 569-594.  
16977320 S.Wiesner, L.E.Wybenga-Groot, N.Warner, H.Lin, T.Pawson, J.D.Forman-Kay, and F.Sicheri (2006).
A change in conformational dynamics underlies the activation of Eph receptor tyrosine kinases.
  EMBO J, 25, 4686-4696.
PDB codes: 2hel 2hen
16607115 W.Dröge (2006).
Redox regulation in anabolic and catabolic processes.
  Curr Opin Clin Nutr Metab Care, 9, 190-195.  
16793764 W.Li, and W.T.Miller (2006).
Role of the activation loop tyrosines in regulation of the insulin-like growth factor I receptor-tyrosine kinase.
  J Biol Chem, 281, 23785-23791.  
16537444 W.Wang, A.Marimuthu, J.Tsai, A.Kumar, H.I.Krupka, C.Zhang, B.Powell, Y.Suzuki, H.Nguyen, M.Tabrizizad, C.Luu, and B.L.West (2006).
Structural characterization of autoinhibited c-Met kinase produced by coexpression in bacteria with phosphatase.
  Proc Natl Acad Sci U S A, 103, 3563-3568.
PDB code: 2g15
16522793 Y.Cheng, Y.Zhang, and J.A.McCammon (2006).
How does activation loop phosphorylation modulate catalytic activity in the cAMP-dependent protein kinase: a theoretical study.
  Protein Sci, 15, 672-683.  
16039863 A.Gangjee, Y.Zeng, M.Ihnat, L.A.Warnke, D.W.Green, R.L.Kisliuk, and F.T.Lin (2005).
Novel 5-substituted, 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors with antiangiogenic and antitumor activity.
  Bioorg Med Chem, 13, 5475-5491.  
15998257 B.J.Goldstein, K.Mahadev, X.Wu, L.Zhu, and H.Motoshima (2005).
Role of insulin-induced reactive oxygen species in the insulin signaling pathway.
  Antioxid Redox Signal, 7, 1021-1031.  
15858616 C.Gambacorti-Passerini, M.Gasser, S.Ahmed, S.Assouline, and L.Scapozza (2005).
Abl inhibitor BMS354825 binding mode in Abelson kinase revealed by molecular docking studies.
  Leukemia, 19, 1267-1269.  
15837193 C.J.Squire, J.M.Dickson, I.Ivanovic, and E.N.Baker (2005).
Structure and inhibition of the human cell cycle checkpoint kinase, Wee1A kinase: an atypical tyrosine kinase with a key role in CDK1 regulation.
  Structure, 13, 541-550.
PDB code: 1x8b
15832311 C.Ortutay, J.Väliaho, K.Stenberg, and M.Vihinen (2005).
KinMutBase: a registry of disease-causing mutations in protein kinase domains.
  Hum Mutat, 25, 435-442.  
16244704 E.D.Scheeff, and P.E.Bourne (2005).
Structural evolution of the protein kinase-like superfamily.
  PLoS Comput Biol, 1, e49.  
15531631 F.Gräter, J.Shen, H.Jiang, M.Gautel, and H.Grubmüller (2005).
Mechanically induced titin kinase activation studied by force-probe molecular dynamics simulations.
  Biophys J, 88, 790-804.  
15647260 G.Zhu, K.Fujii, N.Belkina, Y.Liu, M.James, J.Herrero, and S.Shaw (2005).
Exceptional disfavor for proline at the P + 1 position among AGC and CAMK kinases establishes reciprocal specificity between them and the proline-directed kinases.
  J Biol Chem, 280, 10743-10748.  
15954154 H.Yin, and A.D.Hamilton (2005).
Strategies for targeting protein-protein interactions with synthetic agents.
  Angew Chem Int Ed Engl, 44, 4130-4163.  
16091740 J.Ishiko, M.Mizuki, I.Matsumura, H.Shibayama, H.Sugahara, G.Scholz, H.Serve, and Y.Kanakura (2005).
Roles of tyrosine residues 845, 892 and 922 in constitutive activation of murine FLT3 kinase domain mutant.
  Oncogene, 24, 8144-8153.  
16186108 K.Yang, J.H.Kim, H.J.Kim, I.S.Park, I.Y.Kim, and B.S.Yang (2005).
Tyrosine 740 phosphorylation of discoidin domain receptor 2 by Src stimulates intramolecular autophosphorylation and Shc signaling complex formation.
  J Biol Chem, 280, 39058-39066.  
15893667 M.Lei, M.A.Robinson, and S.C.Harrison (2005).
The active conformation of the PAK1 kinase domain.
  Structure, 13, 769-778.
PDB codes: 1yhv 1yhw
16271895 N.K.Banavali, and B.Roux (2005).
The N-terminal end of the catalytic domain of SRC kinase Hck is a conformational switch implicated in long-range allosteric regulation.
  Structure, 13, 1715-1723.  
16183636 N.LaRonde-LeBlanc, and A.Wlodawer (2005).
A family portrait of the RIO kinases.
  J Biol Chem, 280, 37297-37300.  
15943813 N.LaRonde-LeBlanc, T.Guszczynski, T.Copeland, and A.Wlodawer (2005).
Autophosphorylation of Archaeoglobus fulgidus Rio2 and crystal structures of its nucleotide-metal ion complexes.
  FEBS J, 272, 2800-2810.
PDB codes: 1zao 1zar
16008568 N.Laronde-Leblanc, T.Guszczynski, T.Copeland, and A.Wlodawer (2005).
Structure and activity of the atypical serine kinase Rio1.
  FEBS J, 272, 3698-3713.
PDB codes: 1zp9 1ztf 1zth
16257963 N.Yokoyama, J.Lougheed, and W.T.Miller (2005).
Phosphorylation of WASP by the Cdc42-associated kinase ACK1: dual hydroxyamino acid specificity in a tyrosine kinase.
  J Biol Chem, 280, 42219-42226.  
15611134 P.R.Graves, K.M.Winkfield, and T.A.Haystead (2005).
Regulation of zipper-interacting protein kinase activity in vitro and in vivo by multisite phosphorylation.
  J Biol Chem, 280, 9363-9374.  
16246733 R.S.Depetris, J.Hu, I.Gimpelevich, L.J.Holt, R.J.Daly, and S.R.Hubbard (2005).
Structural basis for inhibition of the insulin receptor by the adaptor protein Grb14.
  Mol Cell, 20, 325-333.
PDB codes: 2aug 2auh
16271887 S.Li, R.S.Depetris, D.Barford, J.Chernoff, and S.R.Hubbard (2005).
Crystal structure of a complex between protein tyrosine phosphatase 1B and the insulin receptor tyrosine kinase.
  Structure, 13, 1643-1651.
PDB code: 2b4s
15939018 S.W.Cowan-Jacob, G.Fendrich, P.W.Manley, W.Jahnke, D.Fabbro, J.Liebetanz, and T.Meyer (2005).
The crystal structure of a c-Src complex in an active conformation suggests possible steps in c-Src activation.
  Structure, 13, 861-871.
PDB code: 1y57
15831699 T.J.Boggon, Y.Li, P.W.Manley, and M.J.Eck (2005).
Crystal structure of the Jak3 kinase domain in complex with a staurosporine analog.
  Blood, 106, 996.
PDB code: 1yvj
15563471 T.L.Schmitt, A.Hotz-Wagenblatt, H.Klein, and W.Dröge (2005).
Interdependent regulation of insulin receptor kinase activity by ADP and hydrogen peroxide.
  J Biol Chem, 280, 3795-3801.  
15950870 T.Pawson, and J.D.Scott (2005).
Protein phosphorylation in signaling--50 years and counting.
  Trends Biochem Sci, 30, 286-290.  
15998262 W.Dröge (2005).
Oxidative enhancement of insulin receptor signaling: experimental findings and clinical implications.
  Antioxid Redox Signal, 7, 1071-1077.  
16305747 X.Lin, M.K.Ayrapetov, and G.Sun (2005).
Characterization of the interactions between the active site of a protein tyrosine kinase and a divalent metal activator.
  BMC Biochem, 6, 25.  
15094157 A.Bennasroune, A.Gardin, D.Aunis, G.Crémel, and P.Hubert (2004).
Tyrosine kinase receptors as attractive targets of cancer therapy.
  Crit Rev Oncol Hematol, 50, 23-38.  
15048100 B.F.Pugh (2004).
Is acetylation the key to opening locked gates?
  Nat Struct Mol Biol, 11, 298-300.  
15314154 C.Duan, H.Yang, M.F.White, and L.Rui (2004).
Disruption of the SH2-B gene causes age-dependent insulin resistance and glucose intolerance.
  Mol Cell Biol, 24, 7435-7443.  
15003245 C.Luo, and P.Laaja (2004).
Inhibitors of JAKs/STATs and the kinases: a possible new cluster of drugs.
  Drug Discov Today, 9, 268-275.  
15308621 J.C.Lougheed, R.H.Chen, P.Mak, and T.J.Stout (2004).
Crystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1.
  J Biol Chem, 279, 44039-44045.
PDB codes: 1u46 1u4d 1u54
15543157 J.F.Ohren, H.Chen, A.Pavlovsky, C.Whitehead, E.Zhang, P.Kuffa, C.Yan, P.McConnell, C.Spessard, C.Banotai, W.T.Mueller, A.Delaney, C.Omer, J.Sebolt-Leopold, D.T.Dudley, I.K.Leung, C.Flamme, J.Warmus, M.Kaufman, S.Barrett, H.Tecle, and C.A.Hasemann (2004).
Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition.
  Nat Struct Mol Biol, 11, 1192-1197.
PDB codes: 1s9i 1s9j
14759363 J.Griffith, J.Black, C.Faerman, L.Swenson, M.Wynn, F.Lu, J.Lippke, and K.Saxena (2004).
The structural basis for autoinhibition of FLT3 by the juxtamembrane domain.
  Mol Cell, 13, 169-178.
PDB code: 1rjb
15130480 K.C.Prutzman, G.Gao, M.L.King, V.V.Iyer, G.A.Mueller, M.D.Schaller, and S.L.Campbell (2004).
The focal adhesion targeting domain of focal adhesion kinase contains a hinge region that modulates tyrosine 926 phosphorylation.
  Structure, 12, 881-891.
PDB code: 1pv3
15465854 K.Moncoq, I.Broutin, C.T.Craescu, P.Vachette, A.Ducruix, and D.Durand (2004).
SAXS study of the PIR domain from the Grb14 molecular adaptor: a natively unfolded protein with a transient structure primer?
  Biophys J, 87, 4056-4064.  
15292186 L.Jin, S.Pluskey, E.C.Petrella, S.M.Cantin, J.C.Gorga, M.J.Rynkiewicz, P.Pandey, J.E.Strickler, R.E.Babine, D.T.Weaver, and K.J.Seidl (2004).
The three-dimensional structure of the ZAP-70 kinase domain in complex with staurosporine: implications for the design of selective inhibitors.
  J Biol Chem, 279, 42818-42825.
PDB code: 1u59
14960716 L.M.Iakoucheva, P.Radivojac, C.J.Brown, T.R.O'Connor, J.G.Sikes, Z.Obradovic, and A.K.Dunker (2004).
The importance of intrinsic disorder for protein phosphorylation.
  Nucleic Acids Res, 32, 1037-1049.  
15037518 M.Hirose, Y.Kuroda, S.Sawa, T.Nakagawa, M.Hirata, M.Sakaguchi, and Y.Tanaka (2004).
Suppression of insulin signalling by a synthetic peptide KIFMK suggests the cytoplasmic linker between DIII-S6 and DIV-S1 as a local anaesthetic binding site on the sodium channel.
  Br J Pharmacol, 142, 222-228.  
14570903 M.Y.Niv, H.Rubin, J.Cohen, L.Tsirulnikov, T.Licht, A.Peretzman-Shemer, E.Cna'an, A.Tartakovsky, I.Stein, S.Albeck, I.Weinstein, M.Goldenberg-Furmanov, D.Tobi, E.Cohen, M.Laster, S.A.Ben-Sasson, and H.Reuveni (2004).
Sequence-based design of kinase inhibitors applicable for therapeutics and target identification.
  J Biol Chem, 279, 1242-1255.  
15343278 N.J.Dibb, S.M.Dilworth, and C.D.Mol (2004).
Switching on kinases: oncogenic activation of BRAF and the PDGFR family.
  Nat Rev Cancer, 4, 718-727.  
15576030 R.D.Dixon, Y.Chen, F.Ding, S.D.Khare, K.C.Prutzman, M.D.Schaller, S.L.Campbell, and N.V.Dokholyan (2004).
New insights into FAK signaling and localization based on detection of a FAT domain folding intermediate.
  Structure, 12, 2161-2171.  
14573614 R.D.Meyer, A.J.Singh, and N.Rahimi (2004).
The carboxyl terminus controls ligand-dependent activation of VEGFR-2 and its signaling.
  J Biol Chem, 279, 735-742.  
15507431 S.Atwell, J.M.Adams, J.Badger, M.D.Buchanan, I.K.Feil, K.J.Froning, X.Gao, J.Hendle, K.Keegan, B.C.Leon, H.J.Müller-Dieckmann, V.L.Nienaber, B.W.Noland, K.Post, K.R.Rajashankar, A.Ramos, M.Russell, S.K.Burley, and S.G.Buchanan (2004).
A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase.
  J Biol Chem, 279, 55827-55832.
PDB codes: 1xba 1xbb 1xbc
15173825 S.R.Hubbard (2004).
Juxtamembrane autoinhibition in receptor tyrosine kinases.
  Nat Rev Mol Cell Biol, 5, 464-471.  
15017265 W.C.DeWolf, and S.M.Gaston (2004).
The cell cycle and its relevance to the urologist.
  J Urol, 171, 1674-1681.  
14711813 Y.Kawamoto, K.Takeda, Y.Okuno, Y.Yamakawa, Y.Ito, R.Taguchi, M.Kato, H.Suzuki, M.Takahashi, and I.Nakashima (2004).
Identification of RET autophosphorylation sites by mass spectrometry.
  J Biol Chem, 279, 14213-14224.  
15231819 Y.X.Fan, L.Wong, T.B.Deb, and G.R.Johnson (2004).
Ligand regulates epidermal growth factor receptor kinase specificity: activation increases preference for GAB1 and SHC versus autophosphorylation sites.
  J Biol Chem, 279, 38143-38150.  
14517908 A.Nayeem, S.Krystek, and T.Stouch (2003).
An assessment of protein-ligand binding site polarizability.
  Biopolymers, 70, 201-211.  
14527402 A.W.Burgess, H.S.Cho, C.Eigenbrot, K.M.Ferguson, T.P.Garrett, D.J.Leahy, M.A.Lemmon, M.X.Sliwkowski, C.W.Ward, and S.Yokoyama (2003).
An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors.
  Mol Cell, 12, 541-552.  
14596595 B.E.Aubol, B.Nolen, J.Shaffer, G.Ghosh, and J.A.Adams (2003).
Novel destabilization of nucleotide binding by the gamma phosphate of ATP in the yeast SR protein kinase Sky1p.
  Biochemistry, 42, 12813-12820.  
12573349 C.B.Gambacorti-Passerini, R.H.Gunby, R.Piazza, A.Galietta, R.Rostagno, and L.Scapozza (2003).
Molecular mechanisms of resistance to imatinib in Philadelphia-chromosome-positive leukaemias.
  Lancet Oncol, 4, 75-85.  
12551896 E.G.Stein, R.Ghirlando, and S.R.Hubbard (2003).
Structural basis for dimerization of the Grb10 Src homology 2 domain. Implications for ligand specificity.
  J Biol Chem, 278, 13257-13264.
PDB code: 1nrv
12435730 F.D.Böhmer, L.Karagyozov, A.Uecker, H.Serve, A.Botzki, S.Mahboobi, and S.Dove (2003).
A single amino acid exchange inverts susceptibility of related receptor tyrosine kinases for the ATP site inhibitor STI-571.
  J Biol Chem, 278, 5148-5155.  
12869569 G.Blum, A.Gazit, and A.Levitzki (2003).
Development of new insulin-like growth factor-1 receptor kinase inhibitors using catechol mimics.
  J Biol Chem, 278, 40442-40454.  
14690593 J.Hu, J.Liu, R.Ghirlando, A.R.Saltiel, and S.R.Hubbard (2003).
Structural basis for recruitment of the adaptor protein APS to the activated insulin receptor.
  Mol Cell, 12, 1379-1389.
PDB codes: 1rpy 1rqq
12730587 J.Schlessinger (2003).
Signal transduction. Autoinhibition control.
  Science, 300, 750-752.  
14517899 P.Ruzza, A.Calderan, A.Donella-Deana, B.Biondi, L.Cesaro, A.Osler, S.Elardo, A.Guiotto, L.A.Pinna, and G.Borin (2003).
Conformational constraints of tyrosine in protein tyrosine kinase substrates: Information about preferred bioactive side-chain orientation.
  Biopolymers, 71, 478-488.  
12686600 P.Saharinen, M.Vihinen, and O.Silvennoinen (2003).
Autoinhibition of Jak2 tyrosine kinase is dependent on specific regions in its pseudokinase domain.
  Mol Biol Cell, 14, 1448-1459.  
14657361 S.Lee, X.Lin, N.H.Nam, K.Parang, and G.Sun (2003).
Determination of the substrate-docking site of protein tyrosine kinase C-terminal Src kinase.
  Proc Natl Acad Sci U S A, 100, 14707-14712.  
12707268 S.Li, N.D.Covino, E.G.Stein, J.H.Till, and S.R.Hubbard (2003).
Structural and biochemical evidence for an autoinhibitory role for tyrosine 984 in the juxtamembrane region of the insulin receptor.
  J Biol Chem, 278, 26007-26014.
PDB code: 1p14
12471165 T.Kitamura, C.R.Kahn, and D.Accili (2003).
Insulin receptor knockout mice.
  Annu Rev Physiol, 65, 313-332.  
12551909 X.Espanel, S.Wälchli, T.Rückle, A.Harrenga, M.Huguenin-Reggiani, and R.H.van Huijsduijnen (2003).
Mapping of synergistic components of weakly interacting protein-protein motifs using arrays of paired peptides.
  J Biol Chem, 278, 15162-15167.  
12517337 X.Huang, M.Begley, K.A.Morgenstern, Y.Gu, P.Rose, H.Zhao, and X.Zhu (2003).
Crystal structure of an inactive Akt2 kinase domain.
  Structure, 11, 21-30.
PDB codes: 1mrv 1mry
12686554 X.Lin, S.Lee, and G.Sun (2003).
Functions of the activation loop in Csk protein-tyrosine kinase.
  J Biol Chem, 278, 24072-24077.  
12044161 A.Cook, E.D.Lowe, E.D.Chrysina, V.T.Skamnaki, N.G.Oikonomakos, and L.N.Johnson (2002).
Structural studies on phospho-CDK2/cyclin A bound to nitrate, a transition state analogue: implications for the protein kinase mechanism.
  Biochemistry, 41, 7301-7311.
PDB code: 1gy3
12146964 B.E.Aubol, B.Nolen, D.Vu, G.Ghosh, and J.A.Adams (2002).
Mechanistic insights into Sky1p, a yeast homologue of the mammalian SR protein kinases.
  Biochemistry, 41, 10002-10009.  
12220490 J.H.Till, M.Becerra, A.Watty, Y.Lu, Y.Ma, T.A.Neubert, S.J.Burden, and S.R.Hubbard (2002).
Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation.
  Structure, 10, 1187-1196.
PDB code: 1luf
12196540 J.Stamos, M.X.Sliwkowski, and C.Eigenbrot (2002).
Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor.
  J Biol Chem, 277, 46265-46272.
PDB codes: 1m14 1m17
12191607 K.Parang, and P.A.Cole (2002).
Designing bisubstrate analog inhibitors for protein kinases.
  Pharmacol Ther, 93, 145-157.  
11841936 L.A.Witucki, X.Huang, K.Shah, Y.Liu, S.Kyin, M.J.Eck, and K.M.Shokat (2002).
Mutant tyrosine kinases with unnatural nucleotide specificity retain the structure and phospho-acceptor specificity of the wild-type enzyme.
  Chem Biol, 9, 25-33.
PDB code: 1ksw
11976270 M.Hirose, J.A.Martyn, Y.Kuroda, Y.Marunaka, and Y.Tanaka (2002).
Mechanism of suppression of insulin signalling with lignocaine.
  Br J Pharmacol, 136, 76-80.  
12015977 M.Huse, and J.Kuriyan (2002).
The conformational plasticity of protein kinases.
  Cell, 109, 275-282.  
12204532 N.P.Shah, J.M.Nicoll, B.Nagar, M.E.Gorre, R.L.Paquette, J.Kuriyan, and C.L.Sawyers (2002).
Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia.
  Cancer Cell, 2, 117-125.  
12360255 P.De Meyts, and J.Whittaker (2002).
Structural biology of insulin and IGF1 receptors: implications for drug design.
  Nat Rev Drug Discov, 1, 769-783.  
12191603 R.A.Engh, and D.Bossemeyer (2002).
Structural aspects of protein kinase control-role of conformational flexibility.
  Pharmacol Ther, 93, 99.  
11989718 S.Hati, S.Bhattacharyya, J.V.Price, and A.S.Tracey (2002).
Comparative modeling of the phosphatase and kinase domains of protein tyrosine phosphatase and insulin receptor kinase from Drosophila melanogaster (DPTP61fm), and a computational study of their mutual interactions.
  Biochem Cell Biol, 80, 225-239.  
12138114 S.Munshi, M.Kornienko, D.L.Hall, J.C.Reid, L.Waxman, S.M.Stirdivant, P.L.Darke, and L.C.Kuo (2002).
Crystal structure of the Apo, unactivated insulin-like growth factor-1 receptor kinase. Implication for inhibitor specificity.
  J Biol Chem, 277, 38797-38802.
PDB code: 1m7n
12218050 S.Shackleton, I.Hamer, M.Foti, N.Zumwald, C.Maeder, and J.L.Carpentier (2002).
Role of two dileucine-like motifs in insulin receptor anchoring to microvilli.
  J Biol Chem, 277, 43631-43637.  
12005431 S.T.Arold, M.K.Hoellerer, and M.E.Noble (2002).
The structural basis of localization and signaling by the focal adhesion targeting domain.
  Structure, 10, 319-327.
PDB codes: 1k04 1k05
11726652 V.Béréziat, A.Kasus-Jacobi, D.Perdereau, B.Cariou, J.Girard, and A.F.Burnol (2002).
Inhibition of insulin receptor catalytic activity by the molecular adapter Grb14.
  J Biol Chem, 277, 4845-4852.  
11746695 A.Cavalli, C.Dezi, G.Folkers, L.Scapozza, and M.Recanatini (2001).
Three-dimensional model of the cyclin-dependent kinase 1 (CDK1): Ab initio active site parameters for molecular dynamics studies of CDKS.
  Proteins, 45, 478-485.  
11598120 A.J.Ablooglu, M.Frankel, E.Rusinova, J.B.Ross, and R.A.Kohanski (2001).
Multiple activation loop conformations and their regulatory properties in the insulin receptor's kinase domain.
  J Biol Chem, 276, 46933-46940.  
11148045 A.J.Ablooglu, and R.A.Kohanski (2001).
Activation of the insulin receptor's kinase domain changes the rate-determining step of substrate phosphorylation.
  Biochemistry, 40, 504-513.  
15989528 C.C.Kumar, and V.Madison (2001).
Drugs targeted against protein kinases.
  Expert Opin Emerg Drugs, 6, 303-315.  
11471071 D.Telting, G.C.van der Zon, J.Dorrestijn, and J.A.Maassen (2001).
IRS-1 tyrosine phosphorylation reflects insulin-induced metabolic and mitogenic responses in 3T3-L1 pre-adipocytes.
  Arch Physiol Biochem, 109, 52-62.  
11389851 H.Yamaguchi, M.Matsushita, A.C.Nairn, and J.Kuriyan (2001).
Crystal structure of the atypical protein kinase domain of a TRP channel with phosphotransferase activity.
  Mol Cell, 7, 1047-1057.
PDB codes: 1ia9 1iah 1iaj
11500492 J.Whittaker, A.V.Groth, D.C.Mynarcik, L.Pluzek, V.L.Gadsbøll, and L.J.Whittaker (2001).
Alanine scanning mutagenesis of a type 1 insulin-like growth factor receptor ligand binding site.
  J Biol Chem, 276, 43980-43986.  
11572780 L.E.Wybenga-Groot, B.Baskin, S.H.Ong, J.Tong, T.Pawson, and F.Sicheri (2001).
Structural basis for autoinhibition of the Ephb2 receptor tyrosine kinase by the unphosphorylated juxtamembrane region.
  Cell, 106, 745-757.
PDB code: 1jpa
11568484 M.Balasubramanyam, and V.Mohan (2001).
Orally active insulin mimics: where do we stand now?
  J Biosci, 26, 383-390.  
11390649 M.Frankel, A.J.Ablooglu, J.W.Leone, E.Rusinova, J.B.Ross, R.L.Heinrikson, and R.A.Kohanski (2001).
Intrasteric inhibition of ATP binding is not required to prevent unregulated autophosphorylation or signaling by the insulin receptor.
  Mol Cell Biol, 21, 4197-4207.  
11354004 M.Miller, K.Ginalski, B.Lesyng, N.Nakaigawa, L.Schmidt, and B.Zbar (2001).
Structural basis of oncogenic activation caused by point mutations in the kinase domain of the MET proto-oncogene: modeling studies.
  Proteins, 44, 32-43.  
11248552 N.K.Tonks, and B.G.Neel (2001).
Combinatorial control of the specificity of protein tyrosine phosphatases.
  Curr Opin Cell Biol, 13, 182-195.  
11391566 N.V.Prabhu, S.A.Siddiqui, J.S.McMurray, and B.M.Pettitt (2001).
Structural basis for the activity of pp60(c-src) protein tyrosine kinase inhibitors.
  Biopolymers, 59, 167-179.  
11694888 S.Favelyukis, J.H.Till, S.R.Hubbard, and W.T.Miller (2001).
Structure and autoregulation of the insulin-like growth factor 1 receptor kinase.
  Nat Struct Biol, 8, 1058-1063.
PDB code: 1k3a
11163213 A.Salmeen, J.N.Andersen, M.P.Myers, N.K.Tonks, and D.Barford (2000).
Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B.
  Mol Cell, 6, 1401-1412.
PDB codes: 1g1f 1g1g 1g1h
10933796 A.Y.Jan, E.F.Johnson, A.J.Diamonti, K.L.Carraway III, and K.S.Anderson (2000).
Insights into the HER-2 receptor tyrosine kinase mechanism and substrate specificity using a transient kinetic analysis.
  Biochemistry, 39, 9786-9803.  
11015187 F.P.Ottensmeyer, D.R.Beniac, R.Z.Luo, and C.C.Yip (2000).
Mechanism of transmembrane signaling: insulin binding and the insulin receptor.
  Biochemistry, 39, 12103-12112.  
11123895 G.Blum, A.Gazit, and A.Levitzki (2000).
Substrate competitive inhibitors of IGF-1 receptor kinase.
  Biochemistry, 39, 15705-15712.  
10713986 I.N.Shindyalov, and P.E.Bourne (2000).
An alternative view of protein fold space.
  Proteins, 38, 247-260.  
11057895 J.Schlessinger (2000).
Cell signaling by receptor tyrosine kinases.
  Cell, 103, 211-225.  
10713991 K.A.Denessiouk, and M.S.Johnson (2000).
When fold is not important: a common structural framework for adenine and AMP binding in 12 unrelated protein families.
  Proteins, 38, 310-326.  
10625501 L.Konkol, T.J.Hirai, and J.A.Adams (2000).
Substrate specificity of the oncoprotein v-Fps: site-specific mutagenesis of the putative P+1 pocket.
  Biochemistry, 39, 255-262.  
11080633 L.M.Shewchuk, A.M.Hassell, B.Ellis, W.D.Holmes, R.Davis, E.L.Horne, S.H.Kadwell, D.D.McKee, and J.T.Moore (2000).
Structure of the Tie2 RTK domain: self-inhibition by the nucleotide binding loop, activation loop, and C-terminal tail.
  Structure, 8, 1105-1113.
PDB code: 1fvr
10893547 L.Sun, and G.McMahon (2000).
Inhibition of tumor angiogenesis by synthetic receptor tyrosine kinase inhibitors.
  Drug Discov Today, 5, 344-353.  
10797575 M.Bernier, H.K.Kole, C.Montrose-Rafizadeh, and S.Kole (2000).
Discrete region of the insulin receptor carboxyl terminus plays key role in insulin action.
  J Cell Biochem, 78, 160-169.  
10852716 M.J.Garant, E.Maksimova, C.Montrose-Rafizadeh, W.Lee-Kwon, S.Kole, and M.Bernier (2000).
Cysteine 981 of the human insulin receptor is required for covalent cross-linking between beta-subunit and a thiol-reactive membrane-associated protein.
  Biochemistry, 39, 7178-7187.  
10761933 P.Chen, C.Luo, Y.Deng, K.Ryan, J.Register, S.Margosiak, A.Tempczyk-Russell, B.Nguyen, P.Myers, K.Lundgren, C.C.Kan, and P.M.O'Connor (2000).
The 1.7 A crystal structure of human cell cycle checkpoint kinase Chk1: implications for Chk1 regulation.
  Cell, 100, 681-692.
PDB code: 1ia8
10827454 S.C.Robertson, J.A.Tynan, and D.J.Donoghue (2000).
RTK mutations and human syndromeswhen good receptors turn bad.
  Trends Genet, 16, 265-271.  
10966463 S.R.Hubbard, and J.H.Till (2000).
Protein tyrosine kinase structure and function.
  Annu Rev Biochem, 69, 373-398.  
11052681 T.J.Hirai, I.Tsigelny, and J.A.Adams (2000).
Catalytic assessment of the glycine-rich loop of the v-Fps oncoprotein using site-directed mutagenesis.
  Biochemistry, 39, 13276-13284.  
10988075 T.Schindler, W.Bornmann, P.Pellicena, W.T.Miller, B.Clarkson, and J.Kuriyan (2000).
Structural mechanism for STI-571 inhibition of abelson tyrosine kinase.
  Science, 289, 1938-1942.
PDB code: 1fpu
10852715 V.Noelle, N.Tennagels, and H.W.Klein (2000).
A single substitution of the insulin receptor kinase inhibits serine autophosphorylation in vitro: evidence for an interaction between the C-terminus and the activation loop.
  Biochemistry, 39, 7170-7177.  
10021370 A.G.Ryazanov, K.S.Pavur, and M.V.Dorovkov (1999).
Alpha-kinases: a new class of protein kinases with a novel catalytic domain.
  Curr Biol, 9, R43-R45.  
10454200 A.Levitzki (1999).
Protein tyrosine kinase inhibitors as novel therapeutic agents.
  Pharmacol Ther, 82, 231-239.  
10197447 B.Guerra, and O.G.Issinger (1999).
Protein kinase CK2 and its role in cellular proliferation, development and pathology.
  Electrophoresis, 20, 391-408.  
10320380 B.Zhang, G.Salituro, D.Szalkowski, Z.Li, Y.Zhang, I.Royo, D.Vilella, M.T.Díez, F.Pelaez, C.Ruby, R.L.Kendall, X.Mao, P.Griffin, J.Calaycay, J.R.Zierath, J.V.Heck, R.G.Smith, and D.E.Moller (1999).
Discovery of a small molecule insulin mimetic with antidiabetic activity in mice.
  Science, 284, 974-977.  
10398926 C.B.Post, B.S.Gaul, E.Z.Eisenmesser, and M.L.Schneider (1999).
NMR structure of phospho-tyrosine signaling complexes.
  Med Res Rev, 19, 295-305.  
10574975 C.N.Woldin, F.S.Hing, J.Lee, P.F.Pilch, and G.G.Shipley (1999).
Structural studies of the detergent-solubilized and vesicle-reconstituted insulin receptor.
  J Biol Chem, 274, 34981-34992.  
9990038 D.A.Tice, J.S.Biscardi, A.L.Nickles, and S.J.Parsons (1999).
Mechanism of biological synergy between cellular Src and epidermal growth factor receptor.
  Proc Natl Acad Sci U S A, 96, 1415-1420.  
11225731 E.Schmid, A.Hotz-Wagenblatt, and W.Dröge (1999).
Inhibition of the insulin receptor kinase phosphorylation by nitric oxide: functional and structural aspects.
  Antioxid Redox Signal, 1, 45-53.  
10577253 E.Zwick, P.O.Hackel, N.Prenzel, and A.Ullrich (1999).
The EGF receptor as central transducer of heterologous signalling systems.
  Trends Pharmacol Sci, 20, 408-412.  
10433517 F.H.Nystrom, and M.J.Quon (1999).
Insulin signalling: metabolic pathways and mechanisms for specificity.
  Cell Signal, 11, 563-574.  
10220355 G.Sun, and R.J.Budde (1999).
Substitution studies of the second divalent metal cation requirement of protein tyrosine kinase CSK.
  Biochemistry, 38, 5659-5665.  
9988744 J.H.Till, P.M.Chan, and W.T.Miller (1999).
Engineering the substrate specificity of the Abl tyrosine kinase.
  J Biol Chem, 274, 4995-5003.  
10454194 J.M.Sowadski, L.F.Epstein, L.Lankiewicz, and R.Karlsson (1999).
Conformational diversity of catalytic cores of protein kinases.
  Pharmacol Ther, 82, 157-164.  
10220345 J.Shaffer, and J.A.Adams (1999).
An ATP-linked structural change in protein kinase A precedes phosphoryl transfer under physiological magnesium concentrations.
  Biochemistry, 38, 5572-5581.  
10368301 M.A.McTigue, J.A.Wickersham, C.Pinko, R.E.Showalter, C.V.Parast, A.Tempczyk-Russell, M.R.Gehring, B.Mroczkowski, C.C.Kan, J.E.Villafranca, and K.Appelt (1999).
Crystal structure of the kinase domain of human vascular endothelial growth factor receptor 2: a key enzyme in angiogenesis.
  Structure, 7, 319-330.
PDB code: 1vr2
  10548062 M.Frankel, S.M.Bishop, A.J.Ablooglu, Y.P.Han, and R.A.Kohanski (1999).
Conformational changes in the activation loop of the insulin receptor's kinase domain.
  Protein Sci, 8, 2158-2165.  
10025408 M.Huse, Y.G.Chen, J.Massagué, and J.Kuriyan (1999).
Crystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12.
  Cell, 96, 425-436.
PDB code: 1b6c
9890935 M.P.Czech, and S.Corvera (1999).
Signaling mechanisms that regulate glucose transport.
  J Biol Chem, 274, 1865-1868.  
10572014 M.S.Kalo, and E.B.Pasquale (1999).
Multiple in vivo tyrosine phosphorylation sites in EphB receptors.
  Biochemistry, 38, 14396-14408.  
10085115 N.R.Brown, M.E.Noble, A.M.Lawrie, M.C.Morris, P.Tunnah, G.Divita, L.N.Johnson, and J.A.Endicott (1999).
Effects of phosphorylation of threonine 160 on cyclin-dependent kinase 2 structure and activity.
  J Biol Chem, 274, 8746-8756.
PDB codes: 1b38 1b39
10454199 P.A.Cole, D.Sondhi, and K.Kim (1999).
Chemical approaches to the study of protein tyrosine kinases and their implications for mechanism and inhibitor design.
  Pharmacol Ther, 82, 219-229.  
10037737 R.L.Kendall, R.Z.Rutledge, X.Mao, A.J.Tebben, R.W.Hungate, and K.A.Thomas (1999).
Vascular endothelial growth factor receptor KDR tyrosine kinase activity is increased by autophosphorylation of two activation loop tyrosine residues.
  J Biol Chem, 274, 6453-6460.  
  10454588 R.M.Katso, R.B.Russell, and T.S.Ganesan (1999).
Functional analysis of H-Ryk, an atypical member of the receptor tyrosine kinase family.
  Mol Cell Biol, 19, 6427-6440.  
10500097 R.Plattner, L.Kadlec, K.A.DeMali, A.Kazlauskas, and A.M.Pendergast (1999).
c-Abl is activated by growth factors and Src family kinases and has a role in the cellular response to PDGF.
  Genes Dev, 13, 2400-2411.  
10074361 S.M.Bishop, J.B.Ross, and R.A.Kohanski (1999).
Autophosphorylation dependent destabilization of the insulin receptor kinase domain: tryptophan-1175 reports changes in the catalytic cleft.
  Biochemistry, 38, 3079-3089.  
10092645 S.Mahajan, S.Ghosh, E.A.Sudbeck, Y.Zheng, S.Downs, M.Hupke, and F.M.Uckun (1999).
Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide].
  J Biol Chem, 274, 9587-9599.  
10454192 S.S.Taylor, E.Radzio-Andzelm, Madhusudan, X.Cheng, L.Ten Eyck, and N.Narayana (1999).
Catalytic subunit of cyclic AMP-dependent protein kinase: structure and dynamics of the active site cleft.
  Pharmacol Ther, 82, 133-141.  
10528237 T.A.Williams, P.Longati, L.Pugliese, P.Gual, A.Bardelli, and P.Michieli (1999).
MET(PRC) mutations in the Ron receptor result in upregulation of tyrosine kinase activity and acquisition of oncogenic potential.
  J Cell Physiol, 181, 507-514.  
10360180 T.Schindler, F.Sicheri, A.Pico, A.Gazit, A.Levitzki, and J.Kuriyan (1999).
Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor.
  Mol Cell, 3, 639-648.
PDB code: 1qcf
9892666 U.Gayko, V.Cleghon, T.Copeland, D.K.Morrison, and N.Perrimon (1999).
Synergistic activities of multiple phosphotyrosine residues mediate full signaling from the Drosophila Torso receptor tyrosine kinase.
  Proc Natl Acad Sci U S A, 96, 523-528.  
10545198 V.T.Skamnaki, D.J.Owen, M.E.Noble, E.D.Lowe, G.Lowe, N.G.Oikonomakos, and L.N.Johnson (1999).
Catalytic mechanism of phosphorylase kinase probed by mutational studies.
  Biochemistry, 38, 14718-14730.
PDB code: 1ql6
10360179 W.Xu, A.Doshi, M.Lei, M.J.Eck, and S.C.Harrison (1999).
Crystal structures of c-Src reveal features of its autoinhibitory mechanism.
  Mol Cell, 3, 629-638.
PDB code: 2src
10404594 X.Zhu, J.L.Kim, J.R.Newcomb, P.E.Rose, D.R.Stover, L.M.Toledo, H.Zhao, and K.A.Morgenstern (1999).
Structural analysis of the lymphocyte-specific kinase Lck in complex with non-selective and Src family selective kinase inhibitors.
  Structure, 7, 651-661.
PDB codes: 1qpc 1qpd 1qpe 1qpj
9698376 A.D.Cann, S.M.Bishop, A.J.Ablooglu, and R.A.Kohanski (1998).
Partial activation of the insulin receptor kinase domain by juxtamembrane autophosphorylation.
  Biochemistry, 37, 11289-11300.  
9748281 A.Kasus-Jacobi, D.Perdereau, C.Auzan, E.Clauser, E.Van Obberghen, F.Mauvais-Jarvis, J.Girard, and A.F.Burnol (1998).
Identification of the rat adapter Grb14 as an inhibitor of insulin actions.
  J Biol Chem, 273, 26026-26035.  
9817025, J.J.Wu, and K.S.Lam (1998).
Protein tyrosine kinases: structure, substrate specificity, and drug discovery.
  Biopolymers, 47, 197-223.  
9612082 J.C.Williams, R.K.Wierenga, and M.Saraste (1998).
Insights into Src kinase functions: structural comparisons.
  Trends Biochem Sci, 23, 179-184.  
9857185 M.E.Cunningham, and L.A.Greene (1998).
A function-structure model for NGF-activated TRK.
  EMBO J, 17, 7282-7293.  
9705275 M.Matsushita, and A.C.Nairn (1998).
Characterization of the mechanism of regulation of Ca2+/ calmodulin-dependent protein kinase I by calmodulin and by Ca2+/calmodulin-dependent protein kinase kinase.
  J Biol Chem, 273, 21473-21481.  
9922154 P.Saylor, E.Hanna, and J.A.Adams (1998).
Mutations in the activation loop tyrosine of the oncoprotein v-Fps.
  Biochemistry, 37, 17875-17881.  
9628482 S.Djordjevic, and A.M.Stock (1998).
Chemotaxis receptor recognition by protein methyltransferase CheR.
  Nat Struct Biol, 5, 446-450.
PDB code: 1bc5
9575136 S.R.Hubbard, M.Mohammadi, and J.Schlessinger (1998).
Autoregulatory mechanisms in protein-tyrosine kinases.
  J Biol Chem, 273, 11987-11990.  
9506989 W.He, D.W.Rose, J.M.Olefsky, and T.A.Gustafson (1998).
Grb10 interacts differentially with the insulin receptor, insulin-like growth factor I receptor, and epidermal growth factor receptor via the Grb10 Src homology 2 (SH2) domain and a second novel domain located between the pleckstrin homology and SH2 domains.
  J Biol Chem, 273, 6860-6867.  
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