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Gene Review

PLEK  -  pleckstrin

Homo sapiens

Synonyms: P47, Platelet 47 kDa protein, Pleckstrin, p47
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Disease relevance of PLEK


High impact information on PLEK


Chemical compound and disease context of PLEK


Biological context of PLEK


Anatomical context of PLEK


Associations of PLEK with chemical compounds


Physical interactions of PLEK


Regulatory relationships of PLEK


Other interactions of PLEK

  • A Gbetagamma binding site of GRK2 is localized in the carboxyl-terminal pleckstrin homology domain [34].
  • Heterologous pleckstrin homology domains do not couple IRS-1 to the insulin receptor [35].
  • In one scenario, beta gamma-subunits of G proteins (G beta gamma) activate certain GRKs (beta-adrenergic receptor kinases 1 and 2, or GRK2 and GRK3), via a pleckstrin homology domain in the COOH terminus [36].
  • The effects of these lipids were prevented by two well known G beta gamma-binding proteins, phosducin and GST-beta ARK-(466-689) fusion protein, suggesting that the G beta gamma-binding domain (possibly the pleckstrin homology domain) of the GRKs is also a site for lipid:protein interaction [36].
  • RACK1, a protein kinase C anchoring protein, coordinates the binding of activated protein kinase C and select pleckstrin homology domains in vitro [37].

Analytical, diagnostic and therapeutic context of PLEK

  • Using multiple sequence alignments and phylogenetic tree reconstructions, we find that 6 subfamilies of the DEP domain exist, of which pleckstrin represents a novel and distinct subfamily [16].
  • Molecular cloning of a novel diacylglycerol kinase isozyme with a pleckstrin homology domain and a C-terminal tail similar to those of the EPH family of protein-tyrosine kinases [38].
  • These findings and failure to detect multimers after treatment of the protein with dimethyl suberimidate indicate that P47 normally exists as a monomer [39].
  • Immunofluorescence analysis showed that PLC(eta)2 was localized predominantly to the plasma membrane at resting state via the pleckstrin homology domain [40].
  • We employed a pleckstrin homology domain-containing fluorescent biosensor, phospholipase C partial differential pleckstrin homology domain-enhanced green fluorescent protein, to visualize Ins(1,4,5)P3 dynamics in insulin-secreting MIN6 cells and mouse islets in real time using a video-rate confocal system [41].


  1. Molecular cloning and expression of the major protein kinase C substrate of platelets. Tyers, M., Rachubinski, R.A., Stewart, M.I., Varrichio, A.M., Shorr, R.G., Haslam, R.J., Harley, C.B. Nature (1988) [Pubmed]
  2. Novel regulatory mechanisms for the Dbl family guanine nucleotide exchange factor Cool-2/alpha-Pix. Feng, Q., Baird, D., Cerione, R.A. EMBO J. (2004) [Pubmed]
  3. Evidence that the expression and phosphorylation status of pleckstrin is modulated by Epstein-Barr virus in human B lymphocytes. Kienzle, N., Cross, S., Young, D.B., Misko, I., Sculley, T.B., Abrams, C.S. Blood (1997) [Pubmed]
  4. Association of CBFA2 mutation with decreased platelet PKC-theta and impaired receptor-mediated activation of GPIIb-IIIa and pleckstrin phosphorylation: proteins regulated by CBFA2 play a role in GPIIb-IIIa activation. Sun, L., Mao, G., Rao, A.K. Blood (2004) [Pubmed]
  5. The 3BP2 Adapter Protein Is Required for Optimal B-Cell Activation and Thymus-Independent Type 2 Humoral Response. Chen, G., Dimitriou, I.D., La Rose, J., Ilangumaran, S., Yeh, W.C., Doody, G., Turner, M., Gommerman, J., Rottapel, R. Mol. Cell. Biol. (2007) [Pubmed]
  6. Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease. Züchner, S., Noureddine, M., Kennerson, M., Verhoeven, K., Claeys, K., De Jonghe, P., Merory, J., Oliveira, S.A., Speer, M.C., Stenger, J.E., Walizada, G., Zhu, D., Pericak-Vance, M.A., Nicholson, G., Timmerman, V., Vance, J.M. Nat. Genet. (2005) [Pubmed]
  7. Structure of the IRS-1 PTB domain bound to the juxtamembrane region of the insulin receptor. Eck, M.J., Dhe-Paganon, S., Trüb, T., Nolte, R.T., Shoelson, S.E. Cell (1996) [Pubmed]
  8. Crystal structure at 2.2 A resolution of the pleckstrin homology domain from human dynamin. Ferguson, K.M., Lemmon, M.A., Schlessinger, J., Sigler, P.B. Cell (1994) [Pubmed]
  9. Solution structure of a pleckstrin-homology domain. Yoon, H.S., Hajduk, P.J., Petros, A.M., Olejniczak, E.T., Meadows, R.P., Fesik, S.W. Nature (1994) [Pubmed]
  10. Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphate. Harlan, J.E., Hajduk, P.J., Yoon, H.S., Fesik, S.W. Nature (1994) [Pubmed]
  11. Protein kinase D2 mediates activation of nuclear factor kappaB by Bcr-Abl in Bcr-Abl+ human myeloid leukemia cells. Mihailovic, T., Marx, M., Auer, A., Van Lint, J., Schmid, M., Weber, C., Seufferlein, T. Cancer Res. (2004) [Pubmed]
  12. Escherichia coli K-1 interaction with human brain micro-vascular endothelial cells triggers phospholipase C-gamma1 activation downstream of phosphatidylinositol 3-kinase. Sukumaran, S.K., McNamara, G., Prasadarao, N.V. J. Biol. Chem. (2003) [Pubmed]
  13. Determination of structural requirements and probable regulatory effectors for membrane association of maize sucrose synthase 1. Hardin, S.C., Duncan, K.A., Huber, S.C. Plant Physiol. (2006) [Pubmed]
  14. Platelets from eclampsia patients have reduced membrane microviscosity and lower activities of the signalling enzymes. Koner, B.C., Jain, M., Dash, D. Int. J. Biochem. Cell Biol. (1998) [Pubmed]
  15. Large-scale expression and purification of a soluble form of the pleckstrin homology domain of the human protooncogenic serine/threonine protein kinase PKB (c-akt) in Escherichia coli. Ingley, E., Hemmings, B.A. Protein Expr. Purif. (1999) [Pubmed]
  16. Structure and dynamics of the human pleckstrin DEP domain: distinct molecular features of a novel DEP domain subfamily. Civera, C., Simon, B., Stier, G., Sattler, M., Macias, M.J. Proteins (2005) [Pubmed]
  17. Clinical study on acupuncture treatment of stomach carcinoma pain. Dang, W., Yang, J. Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan / sponsored by All-China Association of Traditional Chinese Medicine, Academy of Traditional Chinese Medicine. (1998) [Pubmed]
  18. Protein kinase C regulates pleckstrin by phosphorylation of sites adjacent to the N-terminal pleckstrin homology domain. Abrams, C.S., Zhao, W., Belmonte, E., Brass, L.F. J. Biol. Chem. (1995) [Pubmed]
  19. Structure and phosphatidylinositol-(3,4)-bisphosphate binding of the C-terminal PH domain of human pleckstrin. Edlich, C., Stier, G., Simon, B., Sattler, M., Muhle-Goll, C. Structure (Camb.) (2005) [Pubmed]
  20. Polarization of chemoattractant receptor signaling during neutrophil chemotaxis. Servant, G., Weiner, O.D., Herzmark, P., Balla, T., Sedat, J.W., Bourne, H.R. Science (2000) [Pubmed]
  21. Regulation of Btk function by a major autophosphorylation site within the SH3 domain. Park, H., Wahl, M.I., Afar, D.E., Turck, C.W., Rawlings, D.J., Tam, C., Scharenberg, A.M., Kinet, J.P., Witte, O.N. Immunity (1996) [Pubmed]
  22. Phosphorylation of platelet pleckstrin activates inositol polyphosphate 5-phosphatase I. Auethavekiat, V., Abrams, C.S., Majerus, P.W. J. Biol. Chem. (1997) [Pubmed]
  23. Mutational analysis of the pleckstrin homology domain of the beta-adrenergic receptor kinase. Differential effects on G beta gamma and phosphatidylinositol 4,5-bisphosphate binding. Touhara, K., Koch, W.J., Hawes, B.E., Lefkowitz, R.J. J. Biol. Chem. (1995) [Pubmed]
  24. The pleckstrin homology and phosphotyrosine binding domains of insulin receptor substrate 1 mediate inhibition of apoptosis by insulin. Yenush, L., Zanella, C., Uchida, T., Bernal, D., White, M.F. Mol. Cell. Biol. (1998) [Pubmed]
  25. The actin filament-associated protein AFAP-110 is an adaptor protein that modulates changes in actin filament integrity. Baisden, J.M., Qian, Y., Zot, H.M., Flynn, D.C. Oncogene (2001) [Pubmed]
  26. The OSBP-related protein family in humans. Lehto, M., Laitinen, S., Chinetti, G., Johansson, M., Ehnholm, C., Staels, B., Ikonen, E., Olkkonen, V.M. J. Lipid Res. (2001) [Pubmed]
  27. The protooncogene TCL1 is an Akt kinase coactivator. Laine, J., Künstle, G., Obata, T., Sha, M., Noguchi, M. Mol. Cell (2000) [Pubmed]
  28. Tyr624 and Tyr628 in insulin receptor substrate-2 mediate its association with the insulin receptor. Sawka-Verhelle, D., Baron, V., Mothe, I., Filloux, C., White, M.F., Van Obberghen, E. J. Biol. Chem. (1997) [Pubmed]
  29. Translocation of pleckstrin requires its phosphorylation and newly formed ligands. Sloan, D.C., Wang, P., Bao, X., Haslam, R.J. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  30. Mechanisms and consequences of activation of protein kinase B/Akt. Downward, J. Curr. Opin. Cell Biol. (1998) [Pubmed]
  31. The complexity of PTEN: mutation, marker and potential target for therapeutic intervention. Steelman, L.S., Bertrand, F.E., McCubrey, J.A. Expert Opin. Ther. Targets (2004) [Pubmed]
  32. Pleckstrin induces cytoskeletal reorganization via a Rac-dependent pathway. Ma, A.D., Abrams, C.S. J. Biol. Chem. (1999) [Pubmed]
  33. Phosphorylated pleckstrin induces cell spreading via an integrin-dependent pathway. Roll, R.L., Bauman, E.M., Bennett, J.S., Abrams, C.S. J. Cell Biol. (2000) [Pubmed]
  34. The amino-terminal domain of G-protein-coupled receptor kinase 2 is a regulatory Gbeta gamma binding site. Eichmann, T., Lorenz, K., Hoffmann, M., Brockmann, J., Krasel, C., Lohse, M.J., Quitterer, U. J. Biol. Chem. (2003) [Pubmed]
  35. Heterologous pleckstrin homology domains do not couple IRS-1 to the insulin receptor. Burks, D.J., Pons, S., Towery, H., Smith-Hall, J., Myers, M.G., Yenush, L., White, M.F. J. Biol. Chem. (1997) [Pubmed]
  36. Lipid-mediated regulation of G protein-coupled receptor kinases 2 and 3. DebBurman, S.K., Ptasienski, J., Boetticher, E., Lomasney, J.W., Benovic, J.L., Hosey, M.M. J. Biol. Chem. (1995) [Pubmed]
  37. RACK1, a protein kinase C anchoring protein, coordinates the binding of activated protein kinase C and select pleckstrin homology domains in vitro. Rodriguez, M.M., Ron, D., Touhara, K., Chen, C.H., Mochly-Rosen, D. Biochemistry (1999) [Pubmed]
  38. Molecular cloning of a novel diacylglycerol kinase isozyme with a pleckstrin homology domain and a C-terminal tail similar to those of the EPH family of protein-tyrosine kinases. Sakane, F., Imai, S., Kai, M., Wada, I., Kanoh, H. J. Biol. Chem. (1996) [Pubmed]
  39. Purification and characterization of the 47,000-dalton protein phosphorylated during degranulation of human platelets. Imaoka, T., Lynham, J.A., Haslam, R.J. J. Biol. Chem. (1983) [Pubmed]
  40. A novel phospholipase C, PLC(eta)2, is a neuron-specific isozyme. Nakahara, M., Shimozawa, M., Nakamura, Y., Irino, Y., Morita, M., Kudo, Y., Fukami, K. J. Biol. Chem. (2005) [Pubmed]
  41. Inositol (1,4,5)-trisphosphate dynamics and intracellular calcium oscillations in pancreatic beta-cells. Tamarina, N.A., Kuznetsov, A., Rhodes, C.J., Bindokas, V.P., Philipson, L.H. Diabetes (2005) [Pubmed]
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