PDBsum entry 2erk

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protein links
Phosphotransferase PDB id
Protein chain
353 a.a. *
Waters ×102
* Residue conservation analysis
PDB id:
Name: Phosphotransferase
Title: Phosphorylated map kinase erk2
Structure: Extracellular signal-regulated kinase 2. Chain: a. Synonym: erk 2, mitogen activated protein kinase 2, map kinase 2. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Cell_line: bl21. Gene: erk2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
2.40Å     R-factor:   0.192     R-free:   0.264
Authors: B.J.Canagarajah,E.J.Goldsmith
Key ref:
B.J.Canagarajah et al. (1997). Activation mechanism of the MAP kinase ERK2 by dual phosphorylation. Cell, 90, 859-869. PubMed id: 9298898 DOI: 10.1016/S0092-8674(00)80351-7
26-Jun-97     Release date:   01-Jul-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P63086  (MK01_RAT) -  Mitogen-activated protein kinase 1
358 a.a.
353 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Mitogen-activated protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitotic spindle   21 terms 
  Biological process     intracellular signal transduction   40 terms 
  Biochemical function     nucleotide binding     15 terms  


DOI no: 10.1016/S0092-8674(00)80351-7 Cell 90:859-869 (1997)
PubMed id: 9298898  
Activation mechanism of the MAP kinase ERK2 by dual phosphorylation.
B.J.Canagarajah, A.Khokhlatchev, M.H.Cobb, E.J.Goldsmith.
The structure of the active form of the MAP kinase ERK2 has been solved, phosphorylated on a threonine and a tyrosine residue within the phosphorylation lip. The lip is refolded, bringing the phosphothreonine and phosphotyrosine into alignment with surface arginine-rich binding sites. Conformational changes occur in the lip and neighboring structures, including the P+1 site, the MAP kinase insertion, the C-terminal extension, and helix C. Domain rotation and remodeling of the proline-directed P+1 specificity pocket account for the activation. The conformation of the P+1 pocket is similar to a second proline-directed kinase, CDK2-CyclinA, thus permitting the origin of this specificity to be defined. Conformational changes outside the lip provide loci at which the state of phosphorylation can be felt by other cellular components.
  Selected figure(s)  
Figure 2.
Figure 2. Electron Density for pThr and pTyrElectron density map, in the vicinity of the phosphorylation lip and the P+1 specificity pocket of ERK2-P2, contoured at 1.2σ and drawn in O ([32]). The map was calculated in X-PLOR ( [9]) using coefficients 2F^o-F^c and model-derived phases for diffraction data between 20 and 2.4 Å. The map corresponding to Gly-180-Thr-188 is yellow; phosphate atoms are green, and ordered water molecules are red spheres.
Figure 3.
Figure 3. Stereo Diagram of the Environment of pThr and pTyr(A) Stereodiagram showing interactions of pThr-183 in ERK2-P2. Two hydrogen bonding networks emanate from pThr-183. In one network, the pThr-183 ligand Arg-68 is hydrogen bonded to Asp-334 in L16, which also interacts with Gln-64 in helix C. In a second network, pThr-183 ligand Arg-170 interacts with Glu-332 in L16 and His-178 in the lip. Arg-146 forms a hydrogen bond with Tyr-203 (an interaction is present in other protein kinases[73]). The water molecules interacting with pThr-183 are shown as cyan spheres.(B) Stereodiagram showing interactions of pTyr-185 in ERK2-P2 and the environment of the P+1 site.
  The above figures are reprinted by permission from Cell Press: Cell (1997, 90, 859-869) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23064647 S.Hughes, F.Elustondo, A.Di Fonzo, F.G.Leroux, A.C.Wong, A.P.Snijders, S.J.Matthews, and P.Cherepanov (2012).
Crystal structure of human CDC7 kinase in complex with its activator DBF4.
  Nat Struct Mol Biol, 19, 1101-1107.
PDB codes: 4f99 4f9a 4f9b 4f9c
21110380 J.L.Yap, S.Worlikar, A.D.Mackerell, P.Shapiro, and S.Fletcher (2011).
Small-Molecule Inhibitors of the ERK Signaling Pathway: Towards Novel Anticancer Therapeutics.
  ChemMedChem, 6, 38-48.  
21185271 M.Coskun, J.Olsen, J.B.Seidelin, and O.H.Nielsen (2011).
MAP kinases in inflammatory bowel disease.
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21409189 S.Y.Lu, Y.J.Jiang, J.W.Zou, and T.X.Wu (2011).
Dissection of the difference between the group I metal ions in inhibiting GSK3β: a computational study.
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20422242 F.K.Yousafzai, N.Al-Kaff, and G.Moore (2010).
The molecular features of chromosome pairing at meiosis: the polyploid challenge using wheat as a reference.
  Funct Integr Genomics, 10, 147-156.  
21203456 J.Umbrasaite, A.Schweighofer, V.Kazanaviciute, Z.Magyar, Z.Ayatollahi, V.Unterwurzacher, C.Choopayak, J.Boniecka, J.A.Murray, L.Bogre, and I.Meskiene (2010).
MAPK phosphatase AP2C3 induces ectopic proliferation of epidermal cells leading to stomata development in Arabidopsis.
  PLoS One, 5, e15357.  
20568963 L.J.Chen, Y.J.Wang, and G.F.Tseng (2010).
Compression alters kinase and phosphatase activity and tau and MAP2 phosphorylation transiently while inducing the fast adaptive dendritic remodeling of underlying cortical neurons.
  J Neurotrauma, 27, 1657-1669.  
20554783 M.H.Kang, and B.W.Banfield (2010).
Pseudorabies virus tegument protein Us2 recruits the mitogen-activated protein kinase extracellular-regulated kinase (ERK) to membranes through interaction with the ERK common docking domain.
  J Virol, 84, 8398-8408.  
20336692 M.Rabiller, M.Getlik, S.Klüter, A.Richters, S.Tückmantel, J.R.Simard, and D.Rauh (2010).
Proteus in the world of proteins: conformational changes in protein kinases.
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20802461 M.Tipping, Y.Kim, P.Kyriakakis, M.Tong, S.Y.Shvartsman, and A.Veraksa (2010).
β-arrestin Kurtz inhibits MAPK and Toll signalling in Drosophila development.
  EMBO J, 29, 3222-3235.  
21134636 R.Akella, X.Min, Q.Wu, K.H.Gardner, and E.J.Goldsmith (2010).
The third conformation of p38α MAP kinase observed in phosphorylated p38α and in solution.
  Structure, 18, 1571-1578.
PDB code: 3p4k
19895503 T.Zhou, L.Commodore, W.S.Huang, Y.Wang, T.K.Sawyer, W.C.Shakespeare, T.Clackson, X.Zhu, and D.C.Dalgarno (2010).
Structural analysis of DFG-in and DFG-out dual Src-Abl inhibitors sharing a common vinyl purine template.
  Chem Biol Drug Des, 75, 18-28.
PDB codes: 3kf4 3kfa
21070949 W.Ma, Y.Shang, Z.Wei, W.Wen, W.Wang, and M.Zhang (2010).
Phosphorylation of DCC by ERK2 is facilitated by direct docking of the receptor P1 domain to the kinase.
  Structure, 18, 1502-1511.
PDB code: 3o71
20981014 Y.Ogawa, Y.Nonaka, T.Goto, E.Ohnishi, T.Hiramatsu, I.Kii, M.Yoshida, T.Ikura, H.Onogi, H.Shibuya, T.Hosoya, N.Ito, and M.Hagiwara (2010).
Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A.
  Nat Commun, 1, 1-9.
PDB codes: 3anq 3anr
19361221 A.G.Turjanski, G.Hummer, and J.S.Gutkind (2009).
How mitogen-activated protein kinases recognize and phosphorylate their targets: A QM/MM study.
  J Am Chem Soc, 131, 6141-6148.  
19805511 A.W.Truman, K.Y.Kim, and D.E.Levin (2009).
Mechanism of Mpk1 mitogen-activated protein kinase binding to the Swi4 transcription factor and its regulation by a novel caffeine-induced phosphorylation.
  Mol Cell Biol, 29, 6449-6461.  
19204278 C.Hyeon, P.A.Jennings, J.A.Adams, and J.N.Onuchic (2009).
Ligand-induced global transitions in the catalytic domain of protein kinase A.
  Proc Natl Acad Sci U S A, 106, 3023-3028.  
19233656 D.F.Brennan, and D.Barford (2009).
Eliminylation: a post-translational modification catalyzed by phosphothreonine lyases.
  Trends Biochem Sci, 34, 108-114.  
19473979 E.Aberg, K.M.Torgersen, B.Johansen, S.M.Keyse, M.Perander, and O.M.Seternes (2009).
Docking of PRAK/MK5 to the Atypical MAPKs ERK3 and ERK4 Defines a Novel MAPK Interaction Motif.
  J Biol Chem, 284, 19392-19401.  
19689374 K.Burkhard, S.Smith, R.Deshmukh, A.D.MacKerell, and P.Shapiro (2009).
Development of extracellular signal-regulated kinase inhibitors.
  Curr Top Med Chem, 9, 678-689.  
19011223 L.Jirmanova, D.N.Sarma, D.Jankovic, P.R.Mittelstadt, and J.D.Ashwell (2009).
Genetic disruption of p38alpha Tyr323 phosphorylation prevents T-cell receptor-mediated p38alpha activation and impairs interferon-gamma production.
  Blood, 113, 2229-2237.  
19424502 M.C.Balasu, L.N.Spiridon, S.Miron, C.T.Craescu, A.J.Scheidig, A.J.Petrescu, and S.E.Szedlacsek (2009).
Interface analysis of the complex between ERK2 and PTP-SL.
  PLoS ONE, 4, e5432.  
19324872 P.R.Mittelstadt, H.Yamaguchi, E.Appella, and J.D.Ashwell (2009).
T cell receptor-mediated activation of p38{alpha} by mono-phosphorylation of the activation loop results in altered substrate specificity.
  J Biol Chem, 284, 15469-15474.  
  19498957 P.Towb, H.Sun, and S.A.Wasserman (2009).
Tube Is an IRAK-4 homolog in a Toll pathway adapted for development and immunity.
  J Innate Immun, 1, 309-321.  
19847302 S.Galli, O.Jahn, R.Hitt, D.Hesse, L.Opitz, U.Plessmann, H.Urlaub, J.J.Poderoso, E.A.Jares-Erijman, and T.M.Jovin (2009).
a new paradigm for mapk: structural interactions of herk1 with mitochondria in HeLa cells.
  PLoS One, 4, e7541.  
19775474 S.L.Lin, L.Y.Yan, X.W.Liang, Z.B.Wang, Z.Y.Wang, J.Qiao, H.Schatten, and Q.Y.Sun (2009).
A novel variant of ER-alpha, ER-alpha36 mediates testosterone-stimulated ERK and Akt activation in endometrial cancer Hec1A cells.
  Reprod Biol Endocrinol, 7, 102.  
19888758 S.Wu, S.Vossius, S.Rahmouni, A.V.Miletic, T.Vang, J.Vazquez-Rodriguez, F.Cerignoli, Y.Arimura, S.Williams, T.Hayes, M.Moutschen, S.Vasile, M.Pellecchia, T.Mustelin, and L.Tautz (2009).
Multidentate small-molecule inhibitors of vaccinia H1-related (VHR) phosphatase decrease proliferation of cervix cancer cells.
  J Med Chem, 52, 6716-6723.
PDB code: 3f81
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
19835659 Y.Dwivedi, H.S.Rizavi, H.Zhang, R.C.Roberts, R.R.Conley, and G.N.Pandey (2009).
Aberrant extracellular signal-regulated kinase (ERK)1/2 signalling in suicide brain: role of ERK kinase 1 (MEK1).
  Int J Neuropsychopharmacol, 12, 1337-1354.  
  19565474 Z.Yao, and R.Seger (2009).
The ERK signaling cascade--views from different subcellular compartments.
  Biofactors, 35, 407-416.  
18410277 C.Lopez-Gines, R.Gil-Benso, R.Benito, M.Mata, J.Pereda, J.Sastre, P.Roldan, J.Gonzalez-Darder, and M.Cerdá-Nicolás (2008).
The activation of ERK1/2 MAP kinases in glioblastoma pathobiology and its relationship with EGFR amplification.
  Neuropathology, 28, 507-515.  
19053285 D.A.Critton, A.Tortajada, G.Stetson, W.Peti, and R.Page (2008).
Structural basis of substrate recognition by hematopoietic tyrosine phosphatase.
  Biochemistry, 47, 13336-13345.
PDB codes: 2hvl 2qdc 2qdm 2qdp 3d42 3d44
18482985 D.L.Sheridan, Y.Kong, S.A.Parker, K.N.Dalby, and B.E.Turk (2008).
Substrate discrimination among mitogen-activated protein kinases through distinct docking sequence motifs.
  J Biol Chem, 283, 19511-19520.  
19105050 F.Chen, A.D.Mackerell, Y.Luo, and P.Shapiro (2008).
Using Caenorhabditis elegans as a model organism for evaluating extracellular signal-regulated kinase docking domain inhibitors.
  J Cell Commun Signal, 2, 81-92.  
18562239 J.W.Ramos (2008).
The regulation of extracellular signal-regulated kinase (ERK) in mammalian cells.
  Int J Biochem Cell Biol, 40, 2707-2719.  
18501927 K.M.Sours, S.C.Kwok, T.Rachidi, T.Lee, A.Ring, A.N.Hoofnagle, K.A.Resing, and N.G.Ahn (2008).
Hydrogen-exchange mass spectrometry reveals activation-induced changes in the conformational mobility of p38alpha MAP kinase.
  J Mol Biol, 379, 1075-1093.  
18083711 M.C.Martin, L.A.Allan, E.J.Mancini, and P.R.Clarke (2008).
The docking interaction of caspase-9 with ERK2 provides a mechanism for the selective inhibitory phosphorylation of caspase-9 at threonine 125.
  J Biol Chem, 283, 3854-3865.  
18543351 S.H.Kim, and S.H.Kim (2008).
Antagonistic effect of EGF on FAK phosphorylation/dephosphorylation in a cell.
  Cell Biochem Funct, 26, 539-547.  
18310079 S.Jacquet, Y.Nishino, S.Kumphune, P.Sicard, J.E.Clark, K.S.Kobayashi, R.A.Flavell, J.Eickhoff, M.Cotten, and M.S.Marber (2008).
The role of RIP2 in p38 MAPK activation in the stressed heart.
  J Biol Chem, 283, 11964-11971.  
18794356 T.Vomastek, M.P.Iwanicki, W.R.Burack, D.Tiwari, D.Kumar, J.T.Parsons, M.J.Weber, and V.K.Nandicoori (2008).
Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction.
  Mol Cell Biol, 28, 6954-6966.  
18829462 V.Levin-Salomon, K.Kogan, N.G.Ahn, O.Livnah, and D.Engelberg (2008).
Isolation of intrinsically active (MEK-independent) variants of the ERK family of mitogen-activated protein (MAP) kinases.
  J Biol Chem, 283, 34500-34510.  
17496919 A.G.Turjanski, J.P.Vaqué, and J.S.Gutkind (2007).
MAP kinases and the control of nuclear events.
  Oncogene, 26, 3240-3253.  
17694525 D.Kuhn, N.Weskamp, E.Hüllermeier, and G.Klebe (2007).
Functional Classification of Protein Kinase Binding Sites Using Cavbase.
  ChemMedChem, 2, 1432-1447.  
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
17521420 J.L.Jiménez, B.Hegemann, J.R.Hutchins, J.M.Peters, and R.Durbin (2007).
A systematic comparative and structural analysis of protein phosphorylation sites based on the mtcPTM database.
  Genome Biol, 8, R90.  
17473844 K.L.Jeffrey, M.Camps, C.Rommel, and C.R.Mackay (2007).
Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses.
  Nat Rev Drug Discov, 6, 391-403.  
17241234 M.Avitzour, R.Diskin, B.Raboy, N.Askari, D.Engelberg, and O.Livnah (2007).
Intrinsically active variants of all human p38 isoforms.
  FEBS J, 274, 963-975.  
18073109 M.Eto, T.Kitazawa, F.Matsuzawa, S.Aikawa, J.A.Kirkbride, N.Isozumi, Y.Nishimura, D.L.Brautigan, and S.Y.Ohki (2007).
Phosphorylation-induced conformational switching of CPI-17 produces a potent myosin phosphatase inhibitor.
  Structure, 15, 1591-1602.
PDB code: 2rlt
17145763 M.Tresini, A.Lorenzini, C.Torres, and V.J.Cristofalo (2007).
Modulation of replicative senescence of diploid human cells by nuclear ERK signaling.
  J Biol Chem, 282, 4136-4151.  
17088247 N.Askari, R.Diskin, M.Avitzour, R.Capone, O.Livnah, and D.Engelberg (2007).
Hyperactive variants of p38alpha induce, whereas hyperactive variants of p38gamma suppress, activating protein 1-mediated transcription.
  J Biol Chem, 282, 91-99.  
17658891 O.Abramczyk, M.A.Rainey, R.Barnes, L.Martin, and K.N.Dalby (2007).
Expanding the repertoire of an ERK2 recruitment site: cysteine footprinting identifies the D-recruitment site as a mediator of Ets-1 binding.
  Biochemistry, 46, 9174-9186.  
17242519 R.Diskin, D.Engelberg, and O.Livnah (2007).
High-resolution diffracting crystals of intrinsically active p38alpha MAP kinase: a case study for low-throughput approaches.
  Acta Crystallogr D Biol Crystallogr, 63, 260-265.  
17597065 S.Bendetz-Nezer, and R.Seger (2007).
Role of non-phosphorylated activation loop residues in determining ERK2 dephosphorylation, activity, and subcellular localization.
  J Biol Chem, 282, 25114-25122.  
17518606 S.H.Kim, and T.Akaike (2007).
Epidermal growth factor signaling for matrix-dependent cell proliferation and differentiation in primary cultured hepatocytes.
  Tissue Eng, 13, 601-609.  
17718712 T.Zhou, L.Parillon, F.Li, Y.Wang, J.Keats, S.Lamore, Q.Xu, W.Shakespeare, D.Dalgarno, and X.Zhu (2007).
Crystal structure of the T315I mutant of AbI kinase.
  Chem Biol Drug Des, 70, 171-181.
PDB codes: 2qoh 2z60
17914234 V.S.Gowri, K.Anamika, S.Gore, and N.Srinivasan (2007).
Analysis on sliding helices and strands in protein structural comparisons: a case study with protein kinases.
  J Biosci, 32, 921-928.  
18060821 Y.Zhu, H.Li, C.Long, L.Hu, H.Xu, L.Liu, S.Chen, D.C.Wang, and F.Shao (2007).
Structural insights into the enzymatic mechanism of the pathogenic MAPK phosphothreonine lyase.
  Mol Cell, 28, 899-913.
PDB codes: 2p1w 2q8y
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.  
17046812 B.Zhou, J.Zhang, S.Liu, S.Reddy, F.Wang, and Z.Y.Zhang (2006).
Mapping ERK2-MKP3 binding interfaces by hydrogen/deuterium exchange mass spectrometry.
  J Biol Chem, 281, 38834-38844.  
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.  
17000106 F.Chen, C.N.Hancock, A.T.Macias, J.Joh, K.Still, S.Zhong, A.D.MacKerell, and P.Shapiro (2006).
Characterization of ATP-independent ERK inhibitors identified through in silico analysis of the active ERK2 structure.
  Bioorg Med Chem Lett, 16, 6281-6287.  
16362034 F.Qiao, B.Harada, H.Song, J.Whitelegge, A.J.Courey, and J.U.Bowie (2006).
Mae inhibits Pointed-P2 transcriptional activity by blocking its MAPK docking site.
  EMBO J, 25, 70-79.  
16935860 I.Bertani, L.Rusconi, F.Bolognese, G.Forlani, B.Conca, L.De Monte, G.Badaracco, N.Landsberger, and C.Kilstrup-Nielsen (2006).
Functional consequences of mutations in CDKL5, an X-linked gene involved in infantile spasms and mental retardation.
  J Biol Chem, 281, 32048-32056.  
16616379 I.F.Mata, W.J.Wedemeyer, M.J.Farrer, J.P.Taylor, and K.A.Gallo (2006).
LRRK2 in Parkinson's disease: protein domains and functional insights.
  Trends Neurosci, 29, 286-293.  
16799472 J.D.Ashwell (2006).
The many paths to p38 mitogen-activated protein kinase activation in the immune system.
  Nat Rev Immunol, 6, 532-540.  
16724058 J.S.Sebolt-Leopold, and J.M.English (2006).
Mechanisms of drug inhibition of signalling molecules.
  Nature, 441, 457-462.  
16684773 K.Schindler, and E.Winter (2006).
Phosphorylation of Ime2 regulates meiotic progression in Saccharomyces cerevisiae.
  J Biol Chem, 281, 18307-18316.  
16702953 L.Huang, M.Watanabe, M.Chikamori, Y.Kido, T.Yamamoto, M.Shibuya, N.Gotoh, and N.Tsuchida (2006).
Unique role of SNT-2/FRS2beta/FRS3 docking/adaptor protein for negative regulation in EGF receptor tyrosine kinase signaling pathways.
  Oncogene, 25, 6457-6466.  
17114285 M.A.Emrick, T.Lee, P.J.Starkey, M.C.Mumby, K.A.Resing, and N.G.Ahn (2006).
The gatekeeper residue controls autoactivation of ERK2 via a pathway of intramolecular connectivity.
  Proc Natl Acad Sci U S A, 103, 18101-18106.  
17156024 M.Mollapour, and P.W.Piper (2006).
Hog1p mitogen-activated protein kinase determines acetic acid resistance in Saccharomyces cerevisiae.
  FEMS Yeast Res, 6, 1274-1280.  
16733250 N.Murakami, W.Xie, R.C.Lu, M.C.Chen-Hwang, A.Wieraszko, and Y.W.Hwang (2006).
Phosphorylation of amphiphysin I by minibrain kinase/dual-specificity tyrosine phosphorylation-regulated kinase, a kinase implicated in Down syndrome.
  J Biol Chem, 281, 23712-23724.  
16917500 R.Jauch, M.K.Cho, S.Jäkel, C.Netter, K.Schreiter, B.Aicher, M.Zweckstetter, H.Jäckle, and M.C.Wahl (2006).
Mitogen-activated protein kinases interacting kinases are autoinhibited by a reprogrammed activation segment.
  EMBO J, 25, 4020-4032.
PDB codes: 2hw6 2hw7
16424299 R.P.Bhattacharyya, A.Reményi, M.C.Good, C.J.Bashor, A.M.Falick, and W.A.Lim (2006).
The Ste5 scaffold allosterically modulates signaling output of the yeast mating pathway.
  Science, 311, 822-826.
PDB codes: 2f49 2f9g 2fa2
16567630 S.Liu, J.P.Sun, B.Zhou, and Z.Y.Zhang (2006).
Structural basis of docking interactions between ERK2 and MAP kinase phosphatase 3.
  Proc Natl Acad Sci U S A, 103, 5326-5331.
PDB code: 2fys
16799155 S.Polychronopoulos, M.Verykokakis, M.N.Yazicioglu, M.Sakarellos-Daitsiotis, M.H.Cobb, and G.Mavrothalassitis (2006).
The transcriptional ETS2 repressor factor associates with active and inactive Erks through distinct FXF motifs.
  J Biol Chem, 281, 25601-25611.  
16765894 T.Zhou, L.Sun, J.Humphreys, and E.J.Goldsmith (2006).
Docking interactions induce exposure of activation loop in the MAP kinase ERK2.
  Structure, 14, 1011-1019.
PDB code: 2gph
16460808 V.V.Gurevich, and E.V.Gurevich (2006).
The structural basis of arrestin-mediated regulation of G-protein-coupled receptors.
  Pharmacol Ther, 110, 465-502.  
16051177 C.A.Dimitri, W.Dowdle, J.P.MacKeigan, J.Blenis, and L.O.Murphy (2005).
Spatially separate docking sites on ERK2 regulate distinct signaling events in vivo.
  Curr Biol, 15, 1319-1324.  
16148006 C.Tárrega, P.Ríos, R.Cejudo-Marín, C.Blanco-Aparicio, L.van den Berk, J.Schepens, W.Hendriks, L.Tabernero, and R.Pulido (2005).
ERK2 shows a restrictive and locally selective mechanism of recognition by its tyrosine phosphatase inactivators not shared by its activator MEK1.
  J Biol Chem, 280, 37885-37894.  
15618230 G.H.Iyer, M.J.Moore, and S.S.Taylor (2005).
Consequences of lysine 72 mutation on the phosphorylation and activation state of cAMP-dependent kinase.
  J Biol Chem, 280, 8800-8807.  
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.
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Crystal structure of the potent natural product inhibitor balanol in complex with the catalytic subunit of cAMP-dependent protein kinase.
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RSK-B, a novel ribosomal S6 kinase family member, is a CREB kinase under dominant control of p38alpha mitogen-activated protein kinase (p38alphaMAPK).
  J Biol Chem, 273, 29661-29671.  
  9585506 F.Gaits, G.Degols, K.Shiozaki, and P.Russell (1998).
Phosphorylation and association with the transcription factor Atf1 regulate localization of Spc1/Sty1 stress-activated kinase in fission yeast.
  Genes Dev, 12, 1464-1473.  
  9566911 F.R.Cross, and K.Levine (1998).
Molecular evolution allows bypass of the requirement for activation loop phosphorylation of the Cdc28 cyclin-dependent kinase.
  Mol Cell Biol, 18, 2923-2931.  
9837920 G.H.May, K.E.Allen, W.Clark, M.Funk, and D.A.Gillespie (1998).
Analysis of the interaction between c-Jun and c-Jun N-terminal kinase in vivo.
  J Biol Chem, 273, 33429-33435.  
9728395 H.D.Madhani, and G.R.Fink (1998).
The control of filamentous differentiation and virulence in fungi.
  Trends Cell Biol, 8, 348-353.  
  9744865 L.Bardwell, J.G.Cook, D.Voora, D.M.Baggott, A.R.Martinez, and J.Thorner (1998).
Repression of yeast Ste12 transcription factor by direct binding of unphosphorylated Kss1 MAPK and its regulation by the Ste7 MEK.
  Genes Dev, 12, 2887-2898.  
9520446 L.Ling, Z.Cao, and D.V.Goeddel (1998).
NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176.
  Proc Natl Acad Sci U S A, 95, 3792-3797.  
9857185 M.E.Cunningham, and L.A.Greene (1998).
A function-structure model for NGF-activated TRK.
  EMBO J, 17, 7282-7293.  
9799732 M.J.Robinson, S.A.Stippec, E.Goldsmith, M.A.White, and M.H.Cobb (1998).
A constitutively active and nuclear form of the MAP kinase ERK2 is sufficient for neurite outgrowth and cell transformation.
  Curr Biol, 8, 1141-1150.  
  9725911 P.Kaldis, A.A.Russo, H.S.Chou, N.P.Pavletich, and M.J.Solomon (1998).
Human and yeast cdk-activating kinases (CAKs) display distinct substrate specificities.
  Mol Biol Cell, 9, 2545-2560.  
  9528799 P.R.Romano, M.T.Garcia-Barrio, X.Zhang, Q.Wang, D.R.Taylor, F.Zhang, C.Herring, M.B.Mathews, J.Qin, and A.G.Hinnebusch (1998).
Autophosphorylation in the activation loop is required for full kinase activity in vivo of human and yeast eukaryotic initiation factor 2alpha kinases PKR and GCN2.
  Mol Cell Biol, 18, 2282-2297.  
9624152 R.J.Gum, M.M.McLaughlin, S.Kumar, Z.Wang, M.J.Bower, J.C.Lee, J.L.Adams, G.P.Livi, E.J.Goldsmith, and P.R.Young (1998).
Acquisition of sensitivity of stress-activated protein kinases to the p38 inhibitor, SB 203580, by alteration of one or more amino acids within the ATP binding pocket.
  J Biol Chem, 273, 15605-15610.  
9857190 R.Pulido, A.Zúñiga, and A.Ullrich (1998).
PTP-SL and STEP protein tyrosine phosphatases regulate the activation of the extracellular signal-regulated kinases ERK1 and ERK2 by association through a kinase interaction motif.
  EMBO J, 17, 7337-7350.  
  9632779 S.Roy, R.A.McPherson, A.Apolloni, J.Yan, A.Lane, J.Clyde-Smith, and J.F.Hancock (1998).
14-3-3 facilitates Ras-dependent Raf-1 activation in vitro and in vivo.
  Mol Cell Biol, 18, 3947-3955.  
  9827991 T.Fox, J.T.Coll, X.Xie, P.J.Ford, U.A.Germann, M.D.Porter, S.Pazhanisamy, M.A.Fleming, V.Galullo, M.S.Su, and K.P.Wilson (1998).
A single amino acid substitution makes ERK2 susceptible to pyridinyl imidazole inhibitors of p38 MAP kinase.
  Protein Sci, 7, 2249-2255.
PDB code: 1pme
9760235 X.Cheng, S.Shaltiel, and S.S.Taylor (1998).
Mapping substrate-induced conformational changes in cAMP-dependent protein kinase by protein footprinting.
  Biochemistry, 37, 14005-14013.  
9707564 X.Cheng, Y.Ma, M.Moore, B.A.Hemmings, and S.S.Taylor (1998).
Phosphorylation and activation of cAMP-dependent protein kinase by phosphoinositide-dependent protein kinase.
  Proc Natl Acad Sci U S A, 95, 9849-9854.  
9739089 X.Xie, Y.Gu, T.Fox, J.T.Coll, M.A.Fleming, W.Markland, P.R.Caron, K.P.Wilson, and M.S.Su (1998).
Crystal structure of JNK3: a kinase implicated in neuronal apoptosis.
  Structure, 6, 983-991.
PDB code: 1jnk
9642252 Y.Kawata, Y.Mizukami, Z.Fujii, T.Sakumura, K.Yoshida, and M.Matsuzaki (1998).
Applied pressure enhances cell proliferation through mitogen-activated protein kinase activation in mesangial cells.
  J Biol Chem, 273, 16905-16912.  
9753691 Z.Wang, B.J.Canagarajah, J.C.Boehm, S.Kassisà, M.H.Cobb, P.R.Young, S.Abdel-Meguid, J.L.Adams, and E.J.Goldsmith (1998).
Structural basis of inhibitor selectivity in MAP kinases.
  Structure, 6, 1117-1128.
PDB codes: 1a9u 1bl6 1bl7 1bmk 3erk 4erk
9393860 H.D.Madhani, C.A.Styles, and G.R.Fink (1997).
MAP kinases with distinct inhibitory functions impart signaling specificity during yeast differentiation.
  Cell, 91, 673-684.  
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