PDBsum entry 1mai

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Signal transduction protein PDB id
Protein chain
119 a.a. *
Waters ×110
* Residue conservation analysis
PDB id:
Name: Signal transduction protein
Title: Structure of the pleckstrin homology domain from phospholipasE C delta in complex with inositol trisphosphate
Structure: PhospholipasE C delta-1. Chain: a. Fragment: pleckstrin homology domain. Engineered: yes. Other_details: complexed with d-myo-inositol-1,4,5- trisphosphate
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.90Å     R-factor:   0.205     R-free:   0.291
Authors: K.M.Ferguson,M.A.Lemmon,J.Schlessinger,P.B.Sigler
Key ref: K.M.Ferguson et al. (1995). Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain. Cell, 83, 1037-1046. PubMed id: 8521504 DOI: 10.1016/0092-8674(95)90219-8
23-May-96     Release date:   08-Nov-96    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P10688  (PLCD1_RAT) -  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1
756 a.a.
119 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Phosphoinositide phospholipase C.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

myo-Inositol Phosphate Metabolism
      Reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
+ H(2)O
1D-myo-inositol 1,4,5-trisphosphate
Bound ligand (Het Group name = I3P)
corresponds exactly
+ diacylglycerol
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     intracellular signal transduction   1 term 
  Biochemical function     phosphatidylinositol phospholipase C activity     1 term  


DOI no: 10.1016/0092-8674(95)90219-8 Cell 83:1037-1046 (1995)
PubMed id: 8521504  
Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain.
K.M.Ferguson, M.A.Lemmon, J.Schlessinger, P.B.Sigler.
The X-ray crystal structure of the high affinity complex between the pleckstrin homology (PH) domain from rat phospholipase C-delta 1 (PLC-delta 1) and inositol-(1,4,5)-trisphosphate (Ins(1,4,5)P3) has been refined to 1.9 A resolution. The domain fold is similar to others of known structure. Ins(1,4,5)P3 binds on the positively charged face of the electrostatically polarized domain, interacting predominantly with the beta 1/beta 2 and beta 3/beta 4 loops. The 4- and 5-phosphate groups of Ins(1,4,5)P3 interact much more extensively than the 1-phosphate. Two amino acids in the PLC-delta 1 PH domain that contact Ins(1,4,5)P3 have counterparts in the Bruton's tyrosine kinase (Btk) PH domain, where mutational changes cause inherited agammaglobulinemia, suggesting a mechanism for loss of function in Btk mutants. Using electrostatics and varying levels of head-group specificity, PH domains may localize and orient signaling proteins, providing a general membrane targeting and regulatory function.

Literature references that cite this PDB file's key reference

  PubMed id Reference
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A novel N-ethyl-N-nitrosourea-induced mutation in phospholipase Cγ2 causes inflammatory arthritis, metabolic defects, and male infertility in vitro in a murine model.
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20230531 A.D.Ebert, M.Laussmann, S.Wegehingel, L.Kaderali, H.Erfle, J.Reichert, J.Lechner, H.D.Beer, R.Pepperkok, and W.Nickel (2010).
Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is essential for unconventional secretion.
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20389282 A.Manford, T.Xia, A.K.Saxena, C.Stefan, F.Hu, S.D.Emr, and Y.Mao (2010).
Crystal structure of the yeast Sac1: implications for its phosphoinositide phosphatase function.
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PDB code: 3lwt
19840028 B.Geny, A.Grassart, M.Manich, G.Chicanne, B.Payrastre, N.Sauvonnet, and M.R.Popoff (2010).
Rac1 inactivation by lethal toxin from Clostridium sordellii modifies focal adhesions upstream of actin depolymerization.
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20396900 D.E.Logothetis, V.I.Petrou, S.K.Adney, and R.Mahajan (2010).
Channelopathies linked to plasma membrane phosphoinositides.
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20585582 K.F.Ahmad, and W.A.Lim (2010).
The minimal autoinhibited unit of the guanine nucleotide exchange factor intersectin.
  PLoS One, 5, e11291.
PDB code: 3jv3
20714465 M.D.Best, H.Zhang, and G.D.Prestwich (2010).
Inositol polyphosphates, diphosphoinositol polyphosphates and phosphatidylinositol polyphosphate lipids: structure, synthesis, and development of probes for studying biological activity.
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Putting G protein-coupled receptor-mediated activation of phospholipase C in the limelight.
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20559318 T.G.Kutateladze (2010).
Translation of the phosphoinositide code by PI effectors.
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19706607 J.M.McKenna, and E.M.Ostap (2009).
Kinetics of the interaction of myo1c with phosphoinositides.
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Phosphorylation of phospholipase C-delta 1 regulates its enzymatic activity.
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  19008549 R.V.Stahelin (2009).
Lipid binding domains: more than simple lipid effectors.
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19536138 Y.Mao, D.M.Balkin, R.Zoncu, K.S.Erdmann, L.Tomasini, F.Hu, M.M.Jin, M.E.Hodsdon, and P.De Camilli (2009).
A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism.
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PDB codes: 2kie 2kig
18573078 B.C.Suh, and B.Hille (2008).
PIP2 is a necessary cofactor for ion channel function: how and why?
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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
18490450 E.Macia, M.Partisani, C.Favard, E.Mortier, P.Zimmermann, M.F.Carlier, P.Gounon, F.Luton, and M.Franco (2008).
The pleckstrin homology domain of the Arf6-specific exchange factor EFA6 localizes to the plasma membrane by interacting with phosphatidylinositol 4,5-bisphosphate and F-actin.
  J Biol Chem, 283, 19836-19844.  
19008404 E.Urano, T.Aoki, Y.Futahashi, T.Murakami, Y.Morikawa, N.Yamamoto, and J.Komano (2008).
Substitution of the myristoylation signal of human immunodeficiency virus type 1 Pr55Gag with the phospholipase C-delta1 pleckstrin homology domain results in infectious pseudovirion production.
  J Gen Virol, 89, 3144-3149.  
18452019 K.Anraku, T.Inoue, K.Sugimoto, T.Morii, Y.Mori, Y.Okamoto, and M.Otsuka (2008).
Design and synthesis of biotinylated inositol phosphates relevant to the biotin-avidin techniques.
  Org Biomol Chem, 6, 1822-1830.  
18216767 M.A.Lemmon (2008).
Membrane recognition by phospholipid-binding domains.
  Nat Rev Mol Cell Biol, 9, 99.  
18691970 S.N.Hicks, M.R.Jezyk, S.Gershburg, J.P.Seifert, T.K.Harden, and J.Sondek (2008).
General and versatile autoinhibition of PLC isozymes.
  Mol Cell, 31, 383-394.
PDB code: 2zkm
18480063 S.Osawa, S.Funamoto, M.Nobuhara, S.Wada-Kakuda, M.Shimojo, S.Yagishita, and Y.Ihara (2008).
Phosphoinositides suppress gamma-secretase in both the detergent-soluble and -insoluble states.
  J Biol Chem, 283, 19283-19292.  
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.
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17588168 A.Rosenhouse-Dantsker, and D.E.Logothetis (2007).
Molecular characteristics of phosphoinositide binding.
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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.  
17254974 F.Martin-Belmonte, A.Gassama, A.Datta, W.Yu, U.Rescher, V.Gerke, and K.Mostov (2007).
PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42.
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17524618 G.Drin, and S.Scarlata (2007).
Stimulation of phospholipase Cbeta by membrane interactions, interdomain movement, and G protein binding--how many ways can you activate an enzyme?
  Cell Signal, 19, 1383-1392.  
17430887 M.Nomikos, A.Mulgrew-Nesbitt, P.Pallavi, G.Mihalyne, I.Zaitseva, K.Swann, F.A.Lai, D.Murray, and S.McLaughlin (2007).
Binding of phosphoinositide-specific phospholipase C-zeta (PLC-zeta) to phospholipid membranes: potential role of an unstructured cluster of basic residues.
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17222180 N.Uekama, T.Sugita, M.Okada, H.Yagisawa, and S.Tuzi (2007).
Phosphatidylserine induces functional and structural alterations of the membrane-associated pleckstrin homology domain of phospholipase C-delta1.
  FEBS J, 274, 177-187.  
17372228 S.Liu, S.Liu, X.Zhu, H.Liang, A.Cao, Z.Chang, and L.Lai (2007).
Nonnatural protein-protein interaction-pair design by key residues grafting.
  Proc Natl Acad Sci U S A, 104, 5330-5335.  
18096806 S.Lutz, A.Shankaranarayanan, C.Coco, M.Ridilla, M.R.Nance, C.Vettel, D.Baltus, C.R.Evelyn, R.R.Neubig, T.Wieland, and J.J.Tesmer (2007).
Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs.
  Science, 318, 1923-1927.
PDB code: 2rgn
17031667 T.Rohacs (2007).
Regulation of TRP channels by PIP(2).
  Pflugers Arch, 453, 753-762.  
17709751 Y.Maréchal, X.Pesesse, Y.Jia, V.Pouillon, D.Pérez-Morga, J.Daniel, S.Izui, P.J.Cullen, O.Leo, H.R.Luo, C.Erneux, and S.Schurmans (2007).
Inositol 1,3,4,5-tetrakisphosphate controls proapoptotic Bim gene expression and survival in B cells.
  Proc Natl Acad Sci U S A, 104, 13978-13983.  
16669615 G.Drin, D.Douguet, and S.Scarlata (2006).
The pleckstrin homology domain of phospholipase Cbeta transmits enzymatic activation through modulation of the membrane-domain orientation.
  Biochemistry, 45, 5712-5724.  
16613842 H.Feng, M.Ren, and C.S.Rubin (2006).
Conserved domains subserve novel mechanisms and functions in DKF-1, a Caenorhabditis elegans protein kinase D.
  J Biol Chem, 281, 17815-17826.  
16616874 J.H.Hurley (2006).
Membrane binding domains.
  Biochim Biophys Acta, 1761, 805-811.  
16369538 M.E.Bulina, D.M.Chudakov, O.V.Britanova, Y.G.Yanushevich, D.B.Staroverov, T.V.Chepurnykh, E.M.Merzlyak, M.A.Shkrob, S.Lukyanov, and K.A.Lukyanov (2006).
A genetically encoded photosensitizer.
  Nat Biotechnol, 24, 95-99.  
17115053 M.R.Jezyk, J.T.Snyder, S.Gershberg, D.K.Worthylake, T.K.Harden, and J.Sondek (2006).
Crystal structure of Rac1 bound to its effector phospholipase C-beta2.
  Nat Struct Mol Biol, 13, 1135-1140.
PDB code: 2fju
16402909 T.K.Harden, and J.Sondek (2006).
Regulation of phospholipase C isozymes by ras superfamily GTPases.
  Annu Rev Pharmacol Toxicol, 46, 355-379.  
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
15666353 E.Procko, and S.R.McColl (2005).
Leukocytes on the move with phosphoinositide 3-kinase and its downstream effectors.
  Bioessays, 27, 153-163.  
16252003 J.Yan, W.Wen, W.Xu, J.F.Long, M.E.Adams, S.C.Froehner, and M.Zhang (2005).
Structure of the split PH domain and distinct lipid-binding properties of the PH-PDZ supramodule of alpha-syntrophin.
  EMBO J, 24, 3985-3995.
PDB codes: 1z86 1z87 2adz
15741173 K.Aoyagi, T.Sugaya, M.Umeda, S.Yamamoto, S.Terakawa, and M.Takahashi (2005).
The activation of exocytotic sites by the formation of phosphatidylinositol 4,5-bisphosphate microdomains at syntaxin clusters.
  J Biol Chem, 280, 17346-17352.  
15688002 K.L.Rossman, C.J.Der, and J.Sondek (2005).
GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors.
  Nat Rev Mol Cell Biol, 6, 167-180.  
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.  
15665133 S.Scarlata (2005).
Determination of the activation volume of PLCbeta by Gbeta gamma-subunits through the use of high hydrostatic pressure.
  Biophys J, 88, 2867-2874.  
15041659 A.Gambhir, G.Hangyás-Mihályné, I.Zaitseva, D.S.Cafiso, J.Wang, D.Murray, S.N.Pentyala, S.O.Smith, and S.McLaughlin (2004).
Electrostatic sequestration of PIP2 on phospholipid membranes by basic/aromatic regions of proteins.
  Biophys J, 86, 2188-2207.  
15023338 J.W.Yu, J.M.Mendrola, A.Audhya, S.Singh, D.Keleti, D.B.DeWald, D.Murray, S.D.Emr, and M.A.Lemmon (2004).
Genome-wide analysis of membrane targeting by S. cerevisiae pleckstrin homology domains.
  Mol Cell, 13, 677-688.  
15140198 J.Yoon, H.T.Leung, S.Lee, C.Geng, Y.Kim, K.Baek, and W.L.Pak (2004).
Specific molecular alterations in the norpA-encoded phospholipase C of Drosophila and their effects on electrophysiological responses in vivo.
  J Neurochem, 89, 998.  
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
15226509 M.K.Higgins, E.Bokma, E.Koronakis, C.Hughes, and V.Koronakis (2004).
Structure of the periplasmic component of a bacterial drug efflux pump.
  Proc Natl Acad Sci U S A, 101, 9994-9999.
PDB code: 1t5e
15331592 R.Kristelly, G.Gao, and J.J.Tesmer (2004).
Structural determinants of RhoA binding and nucleotide exchange in leukemia-associated Rho guanine-nucleotide exchange factor.
  J Biol Chem, 279, 47352-47362.
PDB codes: 1txd 1x86
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
15377393 W.Cai, J.Pei, and N.V.Grishin (2004).
Reconstruction of ancestral protein sequences and its applications.
  BMC Evol Biol, 4, 33.  
12771127 C.Xu, J.Watras, and L.M.Loew (2003).
Kinetic analysis of receptor-activated phosphoinositide turnover.
  J Cell Biol, 161, 779-791.  
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
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.  
12657629 J.T.Snyder, A.U.Singer, M.R.Wing, T.K.Harden, and J.Sondek (2003).
The pleckstrin homology domain of phospholipase C-beta2 as an effector site for Rac.
  J Biol Chem, 278, 21099-21104.  
12518000 M.P.Czech (2003).
Dynamics of phosphoinositides in membrane retrieval and insertion.
  Annu Rev Physiol, 65, 791-815.  
12471042 M.Rajebhosale, S.Greenwood, J.Vidugiriene, A.Jeromin, and S.Hilfiker (2003).
Phosphatidylinositol 4-OH kinase is a downstream target of neuronal calcium sensor-1 in enhancing exocytosis in neuroendocrine cells.
  J Biol Chem, 278, 6075-6084.  
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
12737822 P.C.Stolt, H.Jeon, H.K.Song, J.Herz, M.J.Eck, and S.C.Blacklow (2003).
Origins of peptide selectivity and phosphoinositide binding revealed by structures of disabled-1 PTB domain complexes.
  Structure, 11, 569-579.
PDB codes: 1ntv 1nu2
12939343 P.Grimbert, A.Valanciute, V.Audard, A.Pawlak, S.Le gouvelo, P.Lang, P.Niaudet, A.Bensman, G.Guellaën, and D.Sahali (2003).
Truncation of C-mip (Tc-mip), a new proximal signaling protein, induces c-maf Th2 transcription factor and cytoskeleton reorganization.
  J Exp Med, 198, 797-807.  
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.  
12736268 S.Tuzi, N.Uekama, M.Okada, S.Yamaguchi, H.Saito, and H.Yagisawa (2003).
Structure and dynamics of the phospholipase C-delta1 pleckstrin homology domain located at the lipid bilayer surface.
  J Biol Chem, 278, 28019-28025.  
12606567 T.Boehm, S.Hofer, P.Winklehner, B.Kellersch, C.Geiger, A.Trockenbacher, S.Neyer, H.Fiegl, S.Ebner, L.Ivarsson, R.Schneider, E.Kremmer, C.Heufler, and W.Kolanus (2003).
Attenuation of cell adhesion in lymphocytes is regulated by CYTIP, a protein which mediates signal complex sequestration.
  EMBO J, 22, 1014-1024.  
12761218 Y.Guo, F.Philip, and S.Scarlata (2003).
The Pleckstrin homology domains of phospholipases C-beta and -delta confer activation through a common site.
  J Biol Chem, 278, 29995-30004.  
12086641 C.M.Lopes, H.Zhang, T.Rohacs, T.Jin, J.Yang, and D.E.Logothetis (2002).
Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies.
  Neuron, 34, 933-944.  
12234919 G.Jogl, Y.Shen, D.Gebauer, J.Li, K.Wiegmann, H.Kashkar, M.Krönke, and L.Tong (2002).
Crystal structure of the BEACH domain reveals an unusual fold and extensive association with a novel PH domain.
  EMBO J, 21, 4785-4795.
PDB code: 1mi1
11994273 G.S.Baillie, E.Huston, G.Scotland, M.Hodgkin, I.Gall, A.H.Peden, C.MacKenzie, E.S.Houslay, R.Currie, T.R.Pettitt, A.R.Walmsley, M.J.Wakelam, J.Warwicker, and M.D.Houslay (2002).
TAPAS-1, a novel microdomain within the unique N-terminal region of the PDE4A1 cAMP-specific phosphodiesterase that allows rapid, Ca2+-triggered membrane association with selectivity for interaction with phosphatidic acid.
  J Biol Chem, 277, 28298-28309.  
12442173 I.Bosanac, J.R.Alattia, T.K.Mal, J.Chan, S.Talarico, F.K.Tong, K.I.Tong, F.Yoshikawa, T.Furuichi, M.Iwai, T.Michikawa, K.Mikoshiba, and M.Ikura (2002).
Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand.
  Nature, 420, 696-700.
PDB code: 1n4k
12021265 J.M.Sugars, S.Cellek, M.Manifava, J.Coadwell, and N.T.Ktistakis (2002).
Hierarchy of membrane-targeting signals of phospholipase D1 involving lipid modification of a pleckstrin homology domain.
  J Biol Chem, 277, 29152-29161.  
12097325 J.Wang, A.Gambhir, G.Hangyás-Mihályné, D.Murray, U.Golebiewska, and S.McLaughlin (2002).
Lateral sequestration of phosphatidylinositol 4,5-bisphosphate by the basic effector domain of myristoylated alanine-rich C kinase substrate is due to nonspecific electrostatic interactions.
  J Biol Chem, 277, 34401-34412.  
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.  
12198118 Q.Hong, I.Gutierrez-Aguirre, A.Barlic, P.Malovrh, K.Kristan, Z.Podlesek, P.Macek, D.Turk, J.M.Gonzalez-Manas, J.H.Lakey, and G.Anderluh (2002).
Two-step membrane binding by Equinatoxin II, a pore-forming toxin from the sea anemone, involves an exposed aromatic cluster and a flexible helix.
  J Biol Chem, 277, 41916-41924.  
11927595 R.N.Grishanin, V.A.Klenchin, K.M.Loyet, J.A.Kowalchyk, K.Ann, and T.F.Martin (2002).
Membrane association domains in Ca2+-dependent activator protein for secretion mediate plasma membrane and dense-core vesicle binding required for Ca2+-dependent exocytosis.
  J Biol Chem, 277, 22025-22034.  
  12438123 R.W.Holz, and D.Axelrod (2002).
Localization of phosphatidylinositol 4,5-P(2) important in exocytosis and a quantitative analysis of chromaffin granule motion adjacent to the plasma membrane.
  Ann N Y Acad Sci, 971, 232-243.  
11956215 S.Das, and W.Cho (2002).
Roles of catalytic domain residues in interfacial binding and activation of group IV cytosolic phospholipase A2.
  J Biol Chem, 277, 23838-23846.  
11988466 S.McLaughlin, J.Wang, A.Gambhir, and D.Murray (2002).
PIP(2) and proteins: interactions, organization, and information flow.
  Annu Rev Biophys Biomol Struct, 31, 151-175.  
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.
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IgG Fc receptors.
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A novel all helix fold of the AP180 amino-terminal domain for phosphoinositide binding and clathrin assembly in synaptic vesicle endocytosis.
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PDB code: 1hx8
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Anionic phospholipids, interfacial binding and the regulation of cell functions.
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Mutational analysis of Gbetagamma and phospholipid interaction with G protein-coupled receptor kinase 2.
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10940243 J.H.Hurley, and S.Misra (2000).
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10847681 M.A.Pearson, D.Reczek, A.Bretscher, and P.A.Karplus (2000).
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Rac homologues and compartmentalized phosphatidylinositol 4, 5-bisphosphate act in a common pathway to regulate polar pollen tube growth.
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The disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids.
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A conserved inositol phospholipid binding site within the pleckstrin homology domain of the Gab1 docking protein is required for epithelial morphogenesis.
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Phosphoinositide binding domains: embracing 3-phosphate.
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Structure of the enabled/VASP homology 1 domain-peptide complex: a key component in the spatial control of actin assembly.
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PDB code: 1evh
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A novel phospholipase C delta4 (PLCdelta4) splice variant as a negative regulator of PLC.
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Pleckstrin homology domains interact with filamentous actin.
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10419454 M.H.Hu, E.M.Bauman, R.L.Roll, N.Yeilding, and C.S.Abrams (1999).
Pleckstrin 2, a widely expressed paralog of pleckstrin involved in actin rearrangement.
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The PH superfold: a structural scaffold for multiple functions.
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Peripheral membrane proteins: FYVE sticky fingers.
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Phosphatidylinositol 3-kinase-dependent membrane association of the Bruton's tyrosine kinase pleckstrin homology domain visualized in single living cells.
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Mammalian phosphoinositide-specific phospholipase C.
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Protein kinase Czeta is a negative regulator of protein kinase B activity.
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Crystal structure of the pleckstrin homology-phosphotyrosine binding (PH-PTB) targeting region of insulin receptor substrate 1.
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PDB code: 1qqg
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Crystal structure of a phosphatidylinositol 3-phosphate-specific membrane-targeting motif, the FYVE domain of Vps27p.
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Differential association of the pleckstrin homology domains of phospholipases C-beta 1, C-beta 2, and C-delta 1 with lipid bilayers and the beta gamma subunits of heterotrimeric G proteins.
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Involvement of EF hand motifs in the Ca(2+)-dependent binding of the pleckstrin homology domain to phosphoinositides.
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Inhibition of in vitro endosomal vesicle fusion activity by aminoglycoside antibiotics.
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The synthesis and cellular roles of phosphatidylinositol 4,5-bisphosphate.
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G protein signaling events are activated at the leading edge of chemotactic cells.
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NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ezrin.
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X-linked agammaglobulinemia: lack of mature B lineage cells caused by mutations in the Btk kinase.
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Numb-associated kinase interacts with the phosphotyrosine binding domain of Numb and antagonizes the function of Numb in vivo.
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The pleckstrin homology domains of dynamin isoforms require oligomerization for high affinity phosphoinositide binding.
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The solution structure and dynamics of the pleckstrin homology domain of G protein-coupled receptor kinase 2 (beta-adrenergic receptor kinase 1). A binding partner of Gbetagamma subunits.
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PDB code: 1bak
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Binding of basic peptides to membranes produces lateral domains enriched in the acidic lipids phosphatidylserine and phosphatidylinositol 4,5-bisphosphate: an electrostatic model and experimental results.
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Replacements of single basic amino acids in the pleckstrin homology domain of phospholipase C-delta1 alter the ligand binding, phospholipase activity, and interaction with the plasma membrane.
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G protein-coupled receptor kinases.
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Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav.
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Specific binding of phosphatidylinositol 4,5-bisphosphate to calcium-dependent activator protein for secretion (CAPS), a potential phosphoinositide effector protein for regulated exocytosis.
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PIP2: activator ... or terminator of small G proteins?
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Activation of phospholipase C gamma by PI 3-kinase-induced PH domain-mediated membrane targeting.
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Pleckstrin homology domain as an inositol compound binding module.
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Phospholipid-binding protein domains.
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Pleckstrin homology domains: a common fold with diverse functions.
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9889104 M.Jost, F.Simpson, J.M.Kavran, M.A.Lemmon, and S.L.Schmid (1998).
Phosphatidylinositol-4,5-bisphosphate is required for endocytic coated vesicle formation.
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Families of phosphoinositide-specific phospholipase C: structure and function.
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Group IV cytosolic phospholipase A2 binds with high affinity and specificity to phosphatidylinositol 4,5-bisphosphate resulting in dramatic increases in activity.
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Catalytic domain of phosphoinositide-specific phospholipase C (PLC). Mutational analysis of residues within the active site and hydrophobic ridge of plcdelta1.
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Visualization of phosphoinositides that bind pleckstrin homology domains: calcium- and agonist-induced dynamic changes and relationship to myo-[3H]inositol-labeled phosphoinositide pools.
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Inositol phospholipids: translocation, translocation, translocation...
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The Grb7 family of signalling proteins.
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A conserved motif in the tail domain of vinculin mediates association with and insertion into acidic phospholipid bilayers.
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9870661 R.Setoguchi, T.Kinashi, H.Sagara, K.Hirosawa, and K.Takatsu (1998).
Defective degranulation and calcium mobilization of bone-marrow derived mast cells from Xid and Btk-deficient mice.
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A phosphoinositide-binding sequence is shared by PH domain target molecules--a model for the binding of PH domains to proteins.
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Identification and analysis of PH domain-containing targets of phosphatidylinositol 3-kinase using a novel in vivo assay in yeast.
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Phosphoinositide lipids as signaling molecules: common themes for signal transduction, cytoskeletal regulation, and membrane trafficking.
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The pleckstrin homology domain of oxysterol-binding protein recognises a determinant specific to Golgi membranes.
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Receptor-induced transient reduction in plasma membrane PtdIns(4,5)P2 concentration monitored in living cells.
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Functional coupling of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate receptor.
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Structure of type IIbeta phosphatidylinositol phosphate kinase: a protein kinase fold flattened for interfacial phosphorylation.
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PDB code: 1bo1
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The PH domain and the polybasic c domain of cytohesin-1 cooperate specifically in plasma membrane association and cellular function.
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Pleckstrin associates with plasma membranes and induces the formation of membrane projections: requirements for phosphorylation and the NH2-terminal PH domain.
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A specific product of phosphatidylinositol 3-kinase directly activates the protein kinase Akt through its pleckstrin homology domain.
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Xid and Xid-like immunodeficiencies from a signaling point of view.
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N-terminal hydrophobic residues of the G-protein ADP-ribosylation factor-1 insert into membrane phospholipids upon GDP to GTP exchange.
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Cloning of a novel human diacylglycerol kinase (DGKtheta) containing three cysteine-rich domains, a proline-rich region, and a pleckstrin homology domain with an overlapping Ras-associating domain.
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Molecular and structural characterization of five novel mutations in the Bruton's tyrosine kinase gene from patients with X-linked agammaglobulinemia.
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Specific role for the PH domain of dynamin-1 in the regulation of rapid endocytosis in adrenal chromaffin cells.
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G protein beta gamma subunits.
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Phosphoinositide binding specificity among phospholipase C isozymes as determined by photo-cross-linking to novel substrate and product analogs.
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Regulated membrane localization of Tiam1, mediated by the NH2-terminal pleckstrin homology domain, is required for Rac-dependent membrane ruffling and C-Jun NH2-terminal kinase activation.
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Protein kinase C and phospholipase C: bilayer interactions and regulation.
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Phospholipase Cgamma activation and phosphoinositide hydrolysis are essential for embryonal development.
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The solution structure of the pleckstrin homology domain of human SOS1. A possible structural role for the sequential association of diffuse B cell lymphoma and pleckstrin homology domains.
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PDB code: 1awe
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Evidence for a requirement for both phospholipid and phosphotyrosine binding via the Shc phosphotyrosine-binding domain in vivo.
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A comparative analysis of the phosphoinositide binding specificity of pleckstrin homology domains.
  J Biol Chem, 272, 22059-22066.  
  17708952 L.M A, F.M, S.J, and F.K (1997).
Regulatory recruitment of signalling molecules to the cell membrane by pleckstrinhomology domains.
  Trends Cell Biol, 7, 237-242.  
9062102 L.O.Essen, O.Perisic, D.E.Lynch, M.Katan, and R.L.Williams (1997).
A ternary metal binding site in the C2 domain of phosphoinositide-specific phospholipase C-delta1.
  Biochemistry, 36, 2753-2762.
PDB codes: 1djg 1djh 1dji
9048554 L.O.Essen, O.Perisic, M.Katan, Y.Wu, M.F.Roberts, and R.L.Williams (1997).
Structural mapping of the catalytic mechanism for a mammalian phosphoinositide-specific phospholipase C.
  Biochemistry, 36, 1704-1718.
PDB codes: 1djw 1djx 1djy 1djz
9148913 L.Yao, H.Suzuki, K.Ozawa, J.Deng, C.Lehel, H.Fukamachi, W.B.Anderson, Y.Kawakami, and T.Kawakami (1997).
Interactions between protein kinase C and pleckstrin homology domains. Inhibition by phosphatidylinositol 4,5-bisphosphate and phorbol 12-myristate 13-acetate.
  J Biol Chem, 272, 13033-13039.  
9218782 M.Hyvönen, and M.Saraste (1997).
Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: molecular explanations for X-linked agammaglobulinaemia.
  EMBO J, 16, 3396-3404.
PDB code: 1btk
9326643 M.I.Wahl, A.C.Fluckiger, R.M.Kato, H.Park, O.N.Witte, and D.J.Rawlings (1997).
Phosphorylation of two regulatory tyrosine residues in the activation of Bruton's tyrosine kinase via alternative receptors.
  Proc Natl Acad Sci U S A, 94, 11526-11533.  
9135150 R.H.Chen, S.Corbalan-Garcia, and D.Bar-Sagi (1997).
The role of the PH domain in the signal-dependent membrane targeting of Sos.
  EMBO J, 16, 1351-1359.  
9376220 R.M.Scaife, and R.L.Margolis (1997).
The role of the PH domain and SH3 binding domains in dynamin function.
  Cell Signal, 9, 395-401.  
9667855 S.E.Shoelson (1997).
SH2 and PTB domain interactions in tyrosine kinase signal transduction.
  Curr Opin Chem Biol, 1, 227-234.  
  9032245 S.Giorgetti-Peraldi, E.Ottinger, G.Wolf, B.Ye, T.R.Burke, and S.E.Shoelson (1997).
Cellular effects of phosphotyrosine-binding domain inhibitors on insulin receptor signaling and trafficking.
  Mol Cell Biol, 17, 1180-1188.  
9122199 S.Tanaka, T.Ouchi, and H.Hanafusa (1997).
Downstream of Crk adaptor signaling pathway: activation of Jun kinase by v-Crk through the guanine nucleotide exchange protein C3G.
  Proc Natl Acad Sci U S A, 94, 2356-2361.  
8999863 T.J.Kubiseski, Y.M.Chook, W.E.Parris, M.Rozakis-Adcock, and T.Pawson (1997).
High affinity binding of the pleckstrin homology domain of mSos1 to phosphatidylinositol (4,5)-bisphosphate.
  J Biol Chem, 272, 1799-1804.  
9182987 T.T.Chuang, E.Pompili, L.Paolucci, M.Sallese, L.De Gioia, M.Salmona, and A.De Blasi (1997).
Identification of a short sequence highly divergent between beta-adrenergic-receptor kinases 1 and 2 that determines the affinity of binding to betagamma subunits of heterotrimeric guanine-nucleotide-binding regulatory proteins.
  Eur J Biochem, 245, 533-540.  
9242915 W.D.Singer, H.A.Brown, and P.C.Sternweis (1997).
Regulation of eukaryotic phosphatidylinositol-specific phospholipase C and phospholipase D.
  Annu Rev Biochem, 66, 475-509.  
9287165 Y.Wu, O.Perisic, R.L.Williams, M.Katan, and M.F.Roberts (1997).
Phosphoinositide-specific phospholipase C delta1 activity toward micellar substrates, inositol 1,2-cyclic phosphate, and other water-soluble substrates: a sequential mechanism and allosteric activation.
  Biochemistry, 36, 11223-11233.  
9391111 Z.Li, M.I.Wahl, A.Eguinoa, L.R.Stephens, P.T.Hawkins, and O.N.Witte (1997).
Phosphatidylinositol 3-kinase-gamma activates Bruton's tyrosine kinase in concert with Src family kinases.
  Proc Natl Acad Sci U S A, 94, 13820-13825.  
8794006 A.B.Satterthwaite, and O.N.Witte (1996).
Lessons from human genetic variants in the study of B-cell differentiation.
  Curr Opin Immunol, 8, 454-458.  
  8754810 A.Klippel, C.Reinhard, W.M.Kavanaugh, G.Apell, M.A.Escobedo, and L.T.Williams (1996).
Membrane localization of phosphatidylinositol 3-kinase is sufficient to activate multiple signal-transducing kinase pathways.
  Mol Cell Biol, 16, 4117-4127.  
8982277 C.S.Abrams, W.Zhao, and L.F.Brass (1996).
A site of interaction between pleckstrin's PH domains and G beta gamma.
  Biochim Biophys Acta, 1314, 233-238.  
8805586 D.Cowburn (1996).
Adaptors and integrators.
  Structure, 4, 1005-1008.  
  8976547 E.A.Nalefski, and J.J.Falke (1996).
The C2 domain calcium-binding motif: structural and functional diversity.
  Protein Sci, 5, 2375-2390.  
8663526 F.Yoshikawa, M.Morita, T.Monkawa, T.Michikawa, T.Furuichi, and K.Mikoshiba (1996).
Mutational analysis of the ligand binding site of the inositol 1,4,5-trisphosphate receptor.
  J Biol Chem, 271, 18277-18284.  
8630736 H.Park, M.I.Wahl, D.E.Afar, C.W.Turck, D.J.Rawlings, C.Tam, A.M.Scharenberg, J.P.Kinet, and O.N.Witte (1996).
Regulation of Btk function by a major autophosphorylation site within the SH3 domain.
  Immunity, 4, 515-525.  
8955136 J.C.Loijens, and R.A.Anderson (1996).
Type I phosphatidylinositol-4-phosphate 5-kinases are distinct members of this novel lipid kinase family.
  J Biol Chem, 271, 32937-32943.  
8663537 J.Font de Mora, C.Guerrero, D.Mahadevan, J.J.Coque, J.M.Rojas, L.M.Esteban, M.Rebecchi, and E.Santos (1996).
Isolated Sos1 PH domain exhibits germinal vesicle breakdown-inducing activity in Xenopus oocytes.
  J Biol Chem, 271, 18272-18276.  
8805372 J.M.Verdi, R.Schmandt, A.Bashirullah, S.Jacob, R.Salvino, C.G.Craig, A.E.Program, H.D.Lipshitz, and C.J.McGlade (1996).
Mammalian NUMB is an evolutionarily conserved signaling adapter protein that specifies cell fate.
  Curr Biol, 6, 1134-1145.  
8810295 J.W.Lomasney, H.F.Cheng, L.P.Wang, Y.Kuan, S.Liu, S.W.Fesik, and K.King (1996).
Phosphatidylinositol 4,5-bisphosphate binding to the pleckstrin homology domain of phospholipase C-delta1 enhances enzyme activity.
  J Biol Chem, 271, 25316-25326.  
  8947047 K.Salim, M.J.Bottomley, E.Querfurth, M.J.Zvelebil, I.Gout, R.Scaife, R.L.Margolis, R.Gigg, C.I.Smith, P.C.Driscoll, M.D.Waterfield, and G.Panayotou (1996).
Distinct specificity in the recognition of phosphoinositides by the pleckstrin homology domains of dynamin and Bruton's tyrosine kinase.
  EMBO J, 15, 6241-6250.  
8646770 M.A.Lemmon, K.M.Ferguson, and J.Schlessinger (1996).
PH domains: diverse sequences with a common fold recruit signaling molecules to the cell surface.
  Cell, 85, 621-624.  
8650155 M.Andjelković, T.Jakubowicz, P.Cron, X.F.Ming, J.W.Han, and B.A.Hemmings (1996).
Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors.
  Proc Natl Acad Sci U S A, 93, 5699-5704.  
8810315 M.J.Hart, S.Sharma, N.elMasry, R.G.Qiu, P.McCabe, P.Polakis, and G.Bollag (1996).
Identification of a novel guanine nucleotide exchange factor for the Rho GTPase.
  J Biol Chem, 271, 25452-25458.  
8599766 M.M.Zhou, B.Huang, E.T.Olejniczak, R.P.Meadows, S.B.Shuker, M.Miyazaki, T.Trüb, S.E.Shoelson, and S.W.Fesik (1996).
Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1 PTB domain.
  Nat Struct Biol, 3, 388-393.
PDB code: 1irs
8885720 P.T.Mattsson, M.Vihinen, and C.I.Smith (1996).
X-linked agammaglobulinemia (XLA): a genetic tyrosine kinase (Btk) disease.
  Bioessays, 18, 825-834.  
  8756648 R.Buchsbaum, J.B.Telliez, S.Goonesekera, and L.A.Feig (1996).
The N-terminal pleckstrin, coiled-coil, and IQ domains of the exchange factor Ras-GRF act cooperatively to facilitate activation by calcium.
  Mol Cell Biol, 16, 4888-4896.  
8805266 R.Irvine, and P.Cullen (1996).
Inositol phosphates - whither bound? Intracellular signalling.
  Curr Biol, 6, 537-540.  
8647858 R.J.Daly, G.M.Sanderson, P.W.Janes, and R.L.Sutherland (1996).
Cloning and characterization of GRB14, a novel member of the GRB7 gene family.
  J Biol Chem, 271, 12502-12510.  
8994965 R.L.Williams, and M.Katan (1996).
Structural views of phosphoinositide-specific phospholipase C: signalling the way ahead.
  Structure, 4, 1387-1394.  
8798423 S.K.DebBurman, J.Ptasienski, J.L.Benovic, and M.M.Hosey (1996).
G protein-coupled receptor kinase GRK2 is a phospholipid-dependent enzyme that can be conditionally activated by G protein betagamma subunits.
  J Biol Chem, 271, 22552-22562.  
9052864 Y.Kawakami, L.Yao, W.Han, and T.Kawakami (1996).
Tec family protein-tyrosine kinases and pleckstrin homology domains in mast cells.
  Immunol Lett, 54, 113-117.  
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.