PDBsum entry 1fb8

Go to PDB code: 
protein ligands links
Signaling protein PDB id
Protein chain
106 a.a. *
PO4 ×2
Waters ×28
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Structure of the pleckstrin homology domain from dapp1/phish
Structure: Dual adaptor of phosphotyrosine and 3-phosphoinos chain: a. Fragment: pleckstrin homology domain. Synonym: dapp1, phish, bam32. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
2.40Å     R-factor:   0.223     R-free:   0.272
Authors: K.M.Ferguson,J.M.Kavran,V.G.Sankaran,E.Fournier,S.J.Isakoff, E.Y.Skolnik,M.A.Lemmon
Key ref:
K.M.Ferguson et al. (2000). Structural basis for discrimination of 3-phosphoinositides by pleckstrin homology domains. Mol Cell, 6, 373-384. PubMed id: 10983984 DOI: 10.1016/S1097-2765(00)00037-X
14-Jul-00     Release date:   20-Jul-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9UN19  (DAPP1_HUMAN) -  Dual adapter for phosphotyrosine and 3-phosphotyrosine and 3-phosphoinositide
280 a.a.
106 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


DOI no: 10.1016/S1097-2765(00)00037-X Mol Cell 6:373-384 (2000)
PubMed id: 10983984  
Structural basis for discrimination of 3-phosphoinositides by pleckstrin homology domains.
K.M.Ferguson, J.M.Kavran, V.G.Sankaran, E.Fournier, S.J.Isakoff, E.Y.Skolnik, M.A.Lemmon.
Pleckstrin homology (PH) domains are protein modules of around 120 amino acids found in many proteins involved in cellular signaling. Certain PH domains drive signal-dependent membrane recruitment of their host proteins by binding strongly and specifically to lipid second messengers produced by agonist-stimulated phosphoinositide 3-kinases (PI 3-Ks). We describe X-ray crystal structures of two different PH domains bound to Ins(1,3,4,5)P4, the head group of the major PI 3-K product PtdIns(3,4,5)P3. One of these PH domains (from Grp1) is PtdIns(3,4,5)P3 specific, while the other (from DAPP1/PHISH) binds strongly to both PtdIns(3,4,5)P3 and its 5'-dephosphorylation product, PtdIns(3,4)P2. Comparison of the two structures provides an explanation for the distinct phosphoinositide specificities of the two PH domains and allows us to predict the 3-phosphoinositide selectivity of uncharacterized PH domains.
  Selected figure(s)  
Figure 1.
Figure 1. DAPP1-PH and Grp1-PH Recognize Distinct Patterns of Phosphate Groups(A) Binding of Ins(1,3,4)P[3] (magenta, squares), and Ins(1,5,6)P[3] (which has the same phosphate arrangement as Ins(3,4,5)P[3]) (cyan, triangles) to DAPP1-PH (left) and Grp1-PH (right) is compared using a ^3H-Ins(1,3,4,5)P[4] competition assay ([17]). DAPP1-PH binds 10-fold more strongly to Ins(1,3,4)P[3] than to the Ins(3,4,5)P[3] analog, while the converse is true for Grp1-PH.(B) Structures of the inositol trisphosphates. Ins(1,3,4)P[3] (magenta) and Ins(3,4,5)P[3] (cyan) are compared. Note that Ins(3,4,5)P[3] is equivalent to Ins(1,5,6)P[3] except in the positioning of the single axial hydroxyl group (2-OH). Ins(3,4,5)P[3] is not commercially available, so Ins(1,5,6)P[3] was used for the experiment shown in (A). Since Ins(3,5,6)P[3] and Ins(1,3,4)P[3] bind identically to DAPP1-PH (Table 1), we suggest that the axial 2-hydroxyl is not likely to be important in defining binding specificity.
Figure 6.
Figure 6. Prediction of PH Domain 3-Phosphoinositide SpecificityPH domains shown to recognize PI 3-kinase products ([15]) are aligned with Grp1-PH and Btk-PH (A) or DAPP1-PH (B), according to whether they are predicted (see text) to make direct side chain contacts with the 5-phosphate of Ins(1,3,4,5)P[4]. Elements of secondary structure are delineated with gray arrows (β strands) or a black bar (the C-terminal α helix). Residues are colored when their side chain is involved in interactions with Ins(1,3,4,5)P[4] in the Btk-PH, Grp1-PH, or DAPP1-PH complex structures. Yellow represents interaction with the 1-phosphate; red, the 3-phosphate; green, the 4-phosphate; and blue, the 5-phosphate. Color coding is predicted for PH domains of unknown structure. The 3-phosphoinositide binding motif ([15]) in the β1/β2 region is also color coded as described above. In (A), PH domains with names underlined are known to select PtdIns(3,4,5)P[3] over PtdIns(3,4)P[2]. Others are predicted to do so. In (B), DAPP1-PH and PKB-PH are both known to bind almost equally to PtdIns(3,4,5)P[3] and PtdIns(3,4)P[2]. Others are predicted to do so.
  The above figures are reprinted by permission from Cell Press: Mol Cell (2000, 6, 373-384) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21310079 S.G.Jackson, S.Al-Saigh, C.Schultz, and M.S.Junop (2011).
Inositol pentakisphosphate isomers bind PH domains with varying specificity and inhibit phosphoinositide interactions.
  BMC Struct Biol, 11, 11.  
21079789 J.Kumar, B.C.Choudhary, R.Metpally, Q.Zheng, M.L.Nonet, S.Ramanathan, D.R.Klopfenstein, and S.P.Koushika (2010).
The Caenorhabditis elegans Kinesin-3 motor UNC-104/KIF1A is degraded upon loss of specific binding to cargo.
  PLoS Genet, 6, e1001200.  
20167601 L.Premkumar, A.A.Bobkov, M.Patel, L.Jaroszewski, L.A.Bankston, B.Stec, K.Vuori, J.F.Côté, and R.C.Liddington (2010).
Structural basis of membrane targeting by the Dock180 family of Rho family guanine exchange factors (Rho-GEFs).
  J Biol Chem, 285, 13211-13222.
PDB code: 3l4c
20559318 T.G.Kutateladze (2010).
Translation of the phosphoinositide code by PI effectors.
  Nat Chem Biol, 6, 507-513.  
19584261 A.Denley, M.Gymnopoulos, S.Kang, C.Mitchell, and P.K.Vogt (2009).
Requirement of phosphatidylinositol(3,4,5)trisphosphate in phosphatidylinositol 3-kinase-induced oncogenic transformation.
  Mol Cancer Res, 7, 1132-1138.  
19666464 F.Campa, H.Y.Yoon, V.L.Ha, Z.Szentpetery, T.Balla, and P.A.Randazzo (2009).
A PH domain in the Arf GTPase-activating protein (GAP) ARAP1 binds phosphatidylinositol 3,4,5-trisphosphate and regulates Arf GAP activity independently of recruitment to the plasma membranes.
  J Biol Chem, 284, 28069-28083.  
19167305 J.D.Knight, and J.J.Falke (2009).
Single-molecule fluorescence studies of a PH domain: new insights into the membrane docking reaction.
  Biophys J, 96, 566-582.  
19346474 M.Guerrero-Valero, C.Ferrer-Orta, J.Querol-Audí, C.Marin-Vicente, I.Fita, J.C.Gómez-Fernández, N.Verdaguer, and S.Corbalán-García (2009).
Structural and mechanistic insights into the association of PKCalpha-C2 domain to PtdIns(4,5)P2.
  Proc Natl Acad Sci U S A, 106, 6603-6607.
PDB code: 3gpe
19290922 R.E.Joseph, and A.H.Andreotti (2009).
Conformational snapshots of Tec kinases during signaling.
  Immunol Rev, 228, 74-92.  
19648926 R.S.Depetris, J.Wu, and S.R.Hubbard (2009).
Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14.
  Nat Struct Mol Biol, 16, 833-839.
PDB code: 3hk0
19620982 S.Tiwari, H.P.Choi, T.Matsuzawa, M.Pypaert, and J.D.MacMicking (2009).
Targeting of the GTPase Irgm1 to the phagosomal membrane via PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3) promotes immunity to mycobacteria.
  Nat Immunol, 10, 907-917.  
19493313 S.V.Madhunapantula, and G.P.Robertson (2009).
The PTEN-AKT3 signaling cascade as a therapeutic target in melanoma.
  Pigment Cell Melanoma Res, 22, 400-419.  
19909369 T.T.Zhang, H.Li, S.M.Cheung, J.L.Costantini, S.Hou, M.Al-Alwan, and A.J.Marshall (2009).
Phosphoinositide 3-kinase-regulated adapters in lymphocyte activation.
  Immunol Rev, 232, 255-272.  
19568789 V.Calleja, M.Laguerre, and B.Larijani (2009).
3-D structure and dynamics of protein kinase B-new mechanism for the allosteric regulation of an AGC kinase.
  J Chem Biol, 2, 11-25.  
19452573 Y.G.Wang, M.Shi, T.Wang, T.Shi, J.Wei, N.Wang, and X.M.Chen (2009).
Signal transduction mechanism of TRB3 in rats with non-alcoholic fatty liver disease.
  World J Gastroenterol, 15, 2329-2335.  
18573078 B.C.Suh, and B.Hille (2008).
PIP2 is a necessary cofactor for ion channel function: how and why?
  Annu Rev Biophys, 37, 175-195.  
18523652 B.E.Steinberg, and S.Grinstein (2008).
Pathogen destruction versus intracellular survival: the role of lipids as phagosomal fate determinants.
  J Clin Invest, 118, 2002-2011.  
  18725531 C.C.Hernandez, O.Zaika, and M.S.Shapiro (2008).
A carboxy-terminal inter-helix linker as the site of phosphatidylinositol 4,5-bisphosphate action on Kv7 (M-type) K+ channels.
  J Gen Physiol, 132, 361-381.  
18838382 C.Huber, A.Mårtensson, G.M.Bokoch, D.Nemazee, and A.L.Gavin (2008).
FGD2, a CDC42-specific Exchange Factor Expressed by Antigen-presenting Cells, Localizes to Early Endosomes and Active Membrane Ruffles.
  J Biol Chem, 283, 34002-34012.  
18768751 D.Komander, M.Patel, M.Laurin, N.Fradet, A.Pelletier, D.Barford, and J.F.Côté (2008).
An alpha-helical extension of the ELMO1 pleckstrin homology domain mediates direct interaction to DOCK180 and is critical in Rac signaling.
  Mol Biol Cell, 19, 4837-4851.
PDB code: 2vsz
18469301 J.He, R.M.Haney, M.Vora, V.V.Verkhusha, R.V.Stahelin, and T.G.Kutateladze (2008).
Molecular mechanism of membrane targeting by the GRP1 PH domain.
  J Lipid Res, 49, 1807-1815.  
18216767 M.A.Lemmon (2008).
Membrane recognition by phospholipid-binding domains.
  Nat Rev Mol Cell Biol, 9, 99.  
18574245 R.M.Klein, C.A.Ufret-Vincenty, L.Hua, and S.E.Gordon (2008).
Determinants of molecular specificity in phosphoinositide regulation. Phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) is the endogenous lipid regulating TRPV1.
  J Biol Chem, 283, 26208-26216.  
18471983 W.S.Park, W.D.Heo, J.H.Whalen, N.A.O'Rourke, H.M.Bryan, T.Meyer, and M.N.Teruel (2008).
Comprehensive identification of PIP3-regulated PH domains from C. elegans to H. sapiens by model prediction and live imaging.
  Mol Cell, 30, 381-392.  
18640982 W.Wen, W.Liu, J.Yan, and M.Zhang (2008).
Structure basis and unconventional lipid membrane binding properties of the PH-C1 tandem of rho kinases.
  J Biol Chem, 283, 26263-26273.  
17588168 A.Rosenhouse-Dantsker, and D.E.Logothetis (2007).
Molecular characteristics of phosphoinositide binding.
  Pflugers Arch, 455, 45-53.  
17339315 D.F.Ceccarelli, I.M.Blasutig, M.Goudreault, Z.Li, J.Ruston, T.Pawson, and F.Sicheri (2007).
Non-canonical interaction of phosphoinositides with pleckstrin homology domains of Tiam1 and ArhGAP9.
  J Biol Chem, 282, 13864-13874.
PDB codes: 2p0d 2p0f 2p0h
17823121 D.Manna, A.Albanese, W.S.Park, and W.Cho (2007).
Mechanistic basis of differential cellular responses of phosphatidylinositol 3,4-bisphosphate- and phosphatidylinositol 3,4,5-trisphosphate-binding pleckstrin homology domains.
  J Biol Chem, 282, 32093-32105.  
17277311 E.E.Kooijman, D.P.Tieleman, C.Testerink, T.Munnik, D.T.Rijkers, K.N.Burger, and Kruijff (2007).
An electrostatic/hydrogen bond switch as the basis for the specific interaction of phosphatidic acid with proteins.
  J Biol Chem, 282, 11356-11364.  
17386267 J.Brognard, E.Sierecki, T.Gao, and A.C.Newton (2007).
PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms.
  Mol Cell, 25, 917-931.  
17502098 J.Li, X.Mao, L.Q.Dong, F.Liu, and L.Tong (2007).
Crystal structures of the BAR-PH and PTB domains of human APPL1.
  Structure, 15, 525-533.
PDB codes: 2ela 2elb
18042453 J.P.DiNitto, A.Delprato, M.T.Gabe Lee, T.C.Cronin, S.Huang, A.Guilherme, M.P.Czech, and D.G.Lambright (2007).
Structural basis and mechanism of autoregulation in 3-phosphoinositide-dependent Grp1 family Arf GTPase exchange factors.
  Mol Cell, 28, 569-583.
PDB codes: 2r09 2r0d
17698854 M.A.Barber, S.Donald, S.Thelen, K.E.Anderson, M.Thelen, and H.C.Welch (2007).
Membrane translocation of P-Rex1 is mediated by G protein betagamma subunits and phosphoinositide 3-kinase.
  J Biol Chem, 282, 29967-29976.  
18034889 S.G.Jackson, Y.Zhang, R.J.Haslam, and M.S.Junop (2007).
Structural analysis of the carboxy terminal PH domain of pleckstrin bound to D-myo-inositol 1,2,3,5,6-pentakisphosphate.
  BMC Struct Biol, 7, 80.
PDB codes: 2i5c 2i5f
17121847 T.Oka, S.Ihara, and Y.Fukui (2007).
Cooperation of DEF6 with activated Rac in regulating cell morphology.
  J Biol Chem, 282, 2011-2018.  
17825589 Y.Jia, K.K.Subramanian, C.Erneux, V.Pouillon, H.Hattori, H.Jo, J.You, D.Zhu, S.Schurmans, and H.R.Luo (2007).
Inositol 1,3,4,5-tetrakisphosphate negatively regulates phosphatidylinositol-3,4,5- trisphosphate signaling in neutrophils.
  Immunity, 27, 453-467.  
16882665 C.Bedet, J.C.Bruusgaard, S.Vergo, L.Groth-Pedersen, S.Eimer, A.Triller, and C.Vannier (2006).
Regulation of gephyrin assembly and glycine receptor synaptic stability.
  J Biol Chem, 281, 30046-30056.  
16615893 H.Teo, D.J.Gill, J.Sun, O.Perisic, D.B.Veprintsev, Y.Vallis, S.D.Emr, and R.L.Williams (2006).
ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes.
  Cell, 125, 99.
PDB codes: 2cay 2caz
16786189 I.Wakamatsu, S.Ihara, and Y.Fukui (2006).
Mutational analysis on the function of the SWAP-70 PH domain.
  Mol Cell Biochem, 293, 137-145.  
16616874 J.H.Hurley (2006).
Membrane binding domains.
  Biochim Biophys Acta, 1761, 805-811.  
16626739 N.Bhardwaj, R.V.Stahelin, R.E.Langlois, W.Cho, and H.Lu (2006).
Structural bioinformatics prediction of membrane-binding proteins.
  J Mol Biol, 359, 486-495.  
16510979 S.G.Jackson, Y.Zhang, X.Bao, K.Zhang, R.Summerfield, R.J.Haslam, and M.S.Junop (2006).
Structure of the carboxy-terminal PH domain of pleckstrin at 2.1 Angstroms.
  Acta Crystallogr D Biol Crystallogr, 62, 324-330.
PDB code: 1zm0
17057716 S.L.Alam, C.Langelier, F.G.Whitby, S.Koirala, H.Robinson, C.P.Hill, and W.I.Sundquist (2006).
Structural basis for ubiquitin recognition by the human ESCRT-II EAP45 GLUE domain.
  Nat Struct Mol Biol, 13, 1029-1030.
PDB code: 2hth
16889899 S.Sebastian, J.Settleman, S.J.Reshkin, A.Azzariti, A.Bellizzi, and A.Paradiso (2006).
The complexity of targeting EGFR signalling in cancer: from expression to turnover.
  Biochim Biophys Acta, 1766, 120-139.  
16500902 W.Wen, J.Yan, and M.Zhang (2006).
Structural characterization of the split pleckstrin homology domain in phospholipase C-gamma1 and its interaction with TRPC3.
  J Biol Chem, 281, 12060-12068.
PDB code: 2fjl
15698571 C.Edlich, G.Stier, B.Simon, M.Sattler, and C.Muhle-Goll (2005).
Structure and phosphatidylinositol-(3,4)-bisphosphate binding of the C-terminal PH domain of human pleckstrin.
  Structure, 13, 277-286.
PDB code: 1xx0
15986137 G.P.Robertson (2005).
Functional and therapeutic significance of Akt deregulation in malignant melanoma.
  Cancer Metastasis Rev, 24, 273-285.  
15784165 G.Song, G.Ouyang, and S.Bao (2005).
The activation of Akt/PKB signaling pathway and cell survival.
  J Cell Mol Med, 9, 59-71.  
16267129 H.Sondermann, B.Nagar, D.Bar-Sagi, and J.Kuriyan (2005).
Computational docking and solution x-ray scattering predict a membrane-interacting role for the histone domain of the Ras activator son of sevenless.
  Proc Natl Acad Sci U S A, 102, 16632-16637.  
15716355 I.Ivetac, A.D.Munday, M.V.Kisseleva, X.M.Zhang, S.Luff, T.Tiganis, J.C.Whisstock, T.Rowe, P.W.Majerus, and C.A.Mitchell (2005).
The type Ialpha inositol polyphosphate 4-phosphatase generates and terminates phosphoinositide 3-kinase signals on endosomes and the plasma membrane.
  Mol Biol Cell, 16, 2218-2233.  
15545267 K.Hill, S.Krugmann, S.R.Andrews, W.J.Coadwell, P.Finan, H.C.Welch, P.T.Hawkins, and L.R.Stephens (2005).
Regulation of P-Rex1 by phosphatidylinositol (3,4,5)-trisphosphate and Gbetagamma subunits.
  J Biol Chem, 280, 4166-4173.  
15689497 M.Fadri, A.Daquinag, S.Wang, T.Xue, and J.Kunz (2005).
The pleckstrin homology domain proteins Slm1 and Slm2 are required for actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-bisphosphate and TORC2.
  Mol Biol Cell, 16, 1883-1900.  
15920473 R.Jin, J.R.Junutula, H.T.Matern, K.E.Ervin, R.H.Scheller, and A.T.Brunger (2005).
Exo84 and Sec5 are competitive regulatory Sec6/8 effectors to the RalA GTPase.
  EMBO J, 24, 2064-2074.
PDB codes: 1zc3 1zc4
15994899 S.Málková, F.Long, R.V.Stahelin, S.V.Pingali, D.Murray, W.Cho, and M.L.Schlossman (2005).
X-ray reflectivity studies of cPLA2{alpha}-C2 domains adsorbed onto Langmuir monolayers of SOPC.
  Biophys J, 89, 1861-1873.  
15808505 T.Gao, F.Furnari, and A.C.Newton (2005).
PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth.
  Mol Cell, 18, 13-24.  
15869386 W.Cho, and R.V.Stahelin (2005).
Membrane-protein interactions in cell signaling and membrane trafficking.
  Annu Rev Biophys Biomol Struct, 34, 119-151.  
15247305 A.Allam, H.Niiro, E.A.Clark, and A.J.Marshall (2004).
The adaptor protein Bam32 regulates Rac1 activation and actin remodeling through a phosphorylation-dependent mechanism.
  J Biol Chem, 279, 39775-39782.  
15271978 A.Roy, and T.P.Levine (2004).
Multiple pools of phosphatidylinositol 4-phosphate detected using the pleckstrin homology domain of Osh2p.
  J Biol Chem, 279, 44683-44689.  
15274927 D.K.Worthylake, K.L.Rossman, and J.Sondek (2004).
Crystal structure of the DH/PH fragment of Dbs without bound GTPase.
  Structure, 12, 1078-1086.
PDB code: 1rj2
15457207 D.Komander, A.Fairservice, M.Deak, G.S.Kular, A.R.Prescott, C.Peter Downes, S.T.Safrany, D.R.Alessi, and D.M.van Aalten (2004).
Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates.
  EMBO J, 23, 3918-3928.
PDB codes: 1w1d 1w1g 1w1h
14747709 D.Komander, M.Deak, N.Morrice, and D.M.van Aalten (2004).
Purification, crystallization and preliminary X-ray diffraction of a proteolytic fragment of PDK1 containing the pleckstrin homology domain.
  Acta Crystallogr D Biol Crystallogr, 60, 314-316.  
15507210 H.Sondermann, S.M.Soisson, S.Boykevisch, S.S.Yang, D.Bar-Sagi, and J.Kuriyan (2004).
Structural analysis of autoinhibition in the Ras activator Son of sevenless.
  Cell, 119, 393-405.
PDB codes: 1xd2 1xd4 1xdv
15199069 K.R.Skowronek, F.Guo, Y.Zheng, and N.Nassar (2004).
The C-terminal basic tail of RhoG assists the guanine nucleotide exchange factor trio in binding to phospholipids.
  J Biol Chem, 279, 37895-37907.
PDB code: 1nty
15459205 M.Hiromura, F.Okada, T.Obata, D.Auguin, T.Shibata, C.Roumestand, and M.Noguchi (2004).
Inhibition of Akt kinase activity by a peptide spanning the betaA strand of the proto-oncogene TCL1.
  J Biol Chem, 279, 53407-53418.  
15103325 S.K.Dove, R.C.Piper, R.K.McEwen, J.W.Yu, M.C.King, D.C.Hughes, J.Thuring, A.B.Holmes, F.T.Cooke, R.H.Michell, P.J.Parker, and M.A.Lemmon (2004).
Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors.
  EMBO J, 23, 1922-1933.  
15456885 S.Xu, Y.Wang, H.Zhao, L.Zhang, W.Xiong, K.W.Yau, H.Hiel, E.Glowatzki, D.K.Ryugo, and D.Valle (2004).
PHR1, a PH domain-containing protein expressed in primary sensory neurons.
  Mol Cell Biol, 24, 9137-9151.  
15359279 T.C.Cronin, J.P.DiNitto, M.P.Czech, and D.G.Lambright (2004).
Structural determinants of phosphoinositide selectivity in splice variants of Grp1 family PH domains.
  EMBO J, 23, 3711-3720.
PDB codes: 1u27 1u29 1u2b
15195146 V.Gervais, V.Lamour, A.Jawhari, F.Frindel, E.Wasielewski, S.Dubaele, J.M.Egly, J.C.Thierry, B.Kieffer, and A.Poterszman (2004).
TFIIH contains a PH domain involved in DNA nucleotide excision repair.
  Nat Struct Mol Biol, 11, 616-622.
PDB code: 1pfj
12783873 A.H.Kim, T.Sasaki, and M.V.Chao (2003).
JNK-interacting protein 1 promotes Akt1 activation.
  J Biol Chem, 278, 29830-29836.  
12764189 D.T.Lodowski, J.A.Pitcher, W.D.Capel, R.J.Lefkowitz, and J.J.Tesmer (2003).
Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma.
  Science, 300, 1256-1262.
PDB code: 1omw
14588241 E.Fournier, S.J.Isakoff, K.Ko, C.J.Cardinale, G.G.Inghirami, Z.Li, M.A.Curotto de Lafaille, and E.Y.Skolnik (2003).
The B cell SH2/PH domain-containing adaptor Bam32/DAPP1 is required for T cell-independent II antigen responses.
  Curr Biol, 13, 1858-1866.  
12885767 G.E.Cozier, D.Bouyoucef, and P.J.Cullen (2003).
Engineering the phosphoinositide-binding profile of a class I pleckstrin homology domain.
  J Biol Chem, 278, 39489-39496.  
  12694559 M.A.Lemmon (2003).
Phosphoinositide recognition domains.
  Traffic, 4, 201-213.  
12518000 M.P.Czech (2003).
Dynamics of phosphoinositides in membrane retrieval and insertion.
  Annu Rev Physiol, 65, 791-815.  
12826668 M.Yun, L.Keshvara, C.G.Park, Y.M.Zhang, J.B.Dickerson, J.Zheng, C.O.Rock, T.Curran, and H.W.Park (2003).
Crystal structures of the Dab homology domains of mouse disabled 1 and 2.
  J Biol Chem, 278, 36572-36581.
PDB codes: 1m7e 1oqn 1p3r
12665569 N.Jones, S.H.Chen, C.Sturk, Z.Master, J.Tran, R.S.Kerbel, and D.J.Dumont (2003).
A unique autophosphorylation site on Tie2/Tek mediates Dok-R phosphotyrosine binding domain binding and function.
  Mol Cell Biol, 23, 2658-2668.  
12925760 P.Hilpelä, P.Oberbanscheidt, P.Hahne, M.Hund, G.Kalhammer, J.V.Small, and M.Bähler (2003).
SWAP-70 identifies a transitional subset of actin filaments in motile cells.
  Mol Biol Cell, 14, 3242-3253.  
12930993 S.M.Singh, and D.Murray (2003).
Molecular modeling of the membrane targeting of phospholipase C pleckstrin homology domains.
  Protein Sci, 12, 1934-1953.  
12670394 V.L.Tybulewicz, L.Ardouin, A.Prisco, and L.F.Reynolds (2003).
Vav1: a key signal transducer downstream of the TCR.
  Immunol Rev, 192, 42-52.  
12376540 V.Paranavitane, W.J.Coadwell, A.Eguinoa, P.T.Hawkins, and L.Stephens (2003).
LL5beta is a phosphatidylinositol (3,4,5)-trisphosphate sensor that can bind the cytoskeletal adaptor, gamma-filamin.
  J Biol Chem, 278, 1328-1335.  
12374806 A.Saxena, P.Morozov, D.Frank, R.Musalo, M.A.Lemmon, E.Y.Skolnik, and B.Tycko (2002).
Phosphoinositide binding by the pleckstrin homology domains of Ipl and Tih1.
  J Biol Chem, 277, 49935-49944.  
12124770 B.Tycko, and I.M.Morison (2002).
Physiological functions of imprinted genes.
  J Cell Physiol, 192, 245-258.  
12176338 C.C.Thomas, M.Deak, D.R.Alessi, and D.M.van Aalten (2002).
High-resolution structure of the pleckstrin homology domain of protein kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate.
  Curr Biol, 12, 1256-1262.
PDB code: 1h10
12208851 D.A.Prober, and B.A.Edgar (2002).
Interactions between Ras1, dMyc, and dPI3K signaling in the developing Drosophila wing.
  Genes Dev, 16, 2286-2299.  
12356722 D.Karathanassis, R.V.Stahelin, J.Bravo, O.Perisic, C.M.Pacold, W.Cho, and R.L.Williams (2002).
Binding of the PX domain of p47(phox) to phosphatidylinositol 3,4-bisphosphate and phosphatidic acid is masked by an intramolecular interaction.
  EMBO J, 21, 5057-5068.
PDB code: 1o7k
12228230 J.L.Zugaza, M.A.López-Lago, M.J.Caloca, M.Dosil, N.Movilla, and X.R.Bustelo (2002).
Structural determinants for the biological activity of Vav proteins.
  J Biol Chem, 277, 45377-45392.  
11889037 K.L.Rossman, D.K.Worthylake, J.T.Snyder, D.P.Siderovski, S.L.Campbell, and J.Sondek (2002).
A crystallographic view of interactions between Dbs and Cdc42: PH domain-assisted guanine nucleotide exchange.
  EMBO J, 21, 1315-1326.
PDB codes: 1kz7 1kzg
12094222 M.Turner, and D.D.Billadeau (2002).
VAV proteins as signal integrators for multi-subunit immune-recognition receptors.
  Nat Rev Immunol, 2, 476-486.  
12019260 P.Várnai, X.Lin, S.B.Lee, G.Tuymetova, T.Bondeva, A.Spät, S.G.Rhee, G.Hajnóczky, and T.Balla (2002).
Inositol lipid binding and membrane localization of isolated pleckstrin homology (PH) domains. Studies on the PH domains of phospholipase C delta 1 and p130.
  J Biol Chem, 277, 27412-27422.  
12086619 P.Zimmermann, K.Meerschaert, G.Reekmans, I.Leenaerts, J.V.Small, J.Vandekerckhove, G.David, and J.Gettemans (2002).
PIP(2)-PDZ domain binding controls the association of syntenin with the plasma membrane.
  Mol Cell, 9, 1215-1225.  
12021278 T.L.Shen, D.C.Han, and J.L.Guan (2002).
Association of Grb7 with phosphoinositides and its role in the regulation of cell migration.
  J Biol Chem, 277, 29069-29077.  
12007412 T.P.Levine, and S.Munro (2002).
Targeting of Golgi-specific pleckstrin homology domains involves both PtdIns 4-kinase-dependent and -independent components.
  Curr Biol, 12, 695-704.  
12177050 T.R.Palmby, K.Abe, and C.J.Der (2002).
Critical role of the pleckstrin homology and cysteine-rich domains in Vav signaling and transforming activity.
  J Biol Chem, 277, 39350-39359.  
12388557 Z.Nie, K.T.Stanley, S.Stauffer, K.M.Jacques, D.S.Hirsch, J.Takei, and P.A.Randazzo (2002).
AGAP1, an endosome-associated, phosphoinositide-dependent ADP-ribosylation factor GTPase-activating protein that affects actin cytoskeleton.
  J Biol Chem, 277, 48965-48975.  
11226253 A.Someya, M.Sata, K.Takeda, G.Pacheco-Rodriguez, V.J.Ferrans, J.Moss, and M.Vaughan (2001).
ARF-GEP(100), a guanine nucleotide-exchange protein for ADP-ribosylation factor 6.
  Proc Natl Acad Sci U S A, 98, 2413-2418.  
11395417 B.Vanhaesebroeck, S.J.Leevers, K.Ahmadi, J.Timms, R.Katso, P.C.Driscoll, R.Woscholski, P.J.Parker, and M.D.Waterfield (2001).
Synthesis and function of 3-phosphorylated inositol lipids.
  Annu Rev Biochem, 70, 535-602.  
11684018 J.Bravo, D.Karathanassis, C.M.Pacold, M.E.Pacold, C.D.Ellson, K.E.Anderson, P.J.Butler, I.Lavenir, O.Perisic, P.T.Hawkins, L.Stephens, and R.L.Williams (2001).
The crystal structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate.
  Mol Cell, 8, 829-839.
PDB code: 1h6h
11248547 J.H.Hurley, and T.Meyer (2001).
Subcellular targeting by membrane lipids.
  Curr Opin Cell Biol, 13, 146-152.  
11577097 J.T.Snyder, K.L.Rossman, M.A.Baumeister, W.M.Pruitt, D.P.Siderovski, C.J.Der, M.A.Lemmon, and J.Sondek (2001).
Quantitative analysis of the effect of phosphoinositide interactions on the function of Dbl family proteins.
  J Biol Chem, 276, 45868-45875.  
11489946 M.Zhao, A.A.Schmitz, Y.Qin, A.Di Cristofano, P.P.Pandolfi, and L.Van Aelst (2001).
Phosphoinositide 3-kinase-dependent membrane recruitment of p62(dok) is essential for its negative effect on mitogen-activated protein (MAP) kinase activation.
  J Exp Med, 194, 265-274.  
11295547 P.A.Randazzo, K.Miura, Z.Nie, A.Orr, A.B.Theibert, and B.G.Kearns (2001).
Cytohesins and centaurins: mediators of PI 3-kinase regulated Arf signaling.
  Trends Biochem Sci, 26, 220-221.  
11737823 S.Corvera (2001).
Phosphatidylinositol 3-kinase and the control of endosome dynamics: new players defined by structural motifs.
  Traffic, 2, 859-866.  
11406365 S.G.Ward, and D.A.Cantrell (2001).
Phosphoinositide 3-kinases in T lymphocyte activation.
  Curr Opin Immunol, 13, 332-338.  
11230696 T.Kutateladze, and M.Overduin (2001).
Structural mechanism of endosome docking by the FYVE domain.
  Science, 291, 1793-1796.
PDB codes: 1hyi 1hyj
11114512 J.H.Hurley, Y.Tsujishita, and M.A.Pearson (2000).
Floundering about at cell membranes: a structural view of phospholipid signaling.
  Curr Opin Struct Biol, 10, 737-743.  
11114537 P.J.Cullen, and P.Chardin (2000).
Membrane targeting: what a difference a G makes.
  Curr Biol, 10, R876-R878.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.