The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Plek  -  pleckstrin

Mus musculus

Synonyms: 2010300B13Rik, Pleckstrin
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Plek

  • 3BP2 is a pleckstrin homology domain- and Src homology 2 (SH2) domain-containing adapter protein that is mutated in the rare human bone disorder cherubism and which has also been implicated in immunoreceptor signaling [1].

High impact information on Plek


Biological context of Plek


Anatomical context of Plek


Associations of Plek with chemical compounds

  • Deletion of the N-terminal region containing the pleckstrin homology domain did not affect RAC-PK activation by okadaic acid, but it reduced vanadate-stimulated activity and also blocked the serum-induced activation [7].
  • The functions of Dok-1 have now been investigated by the generation of two different COOH-terminal truncation mutants of this protein: one (DokPH+PTB) containing the pleckstrin homology and phosphotyrosine-binding domains, and the other (DokPH) composed only of the pleckstrin homology domain [16].
  • The feasibility of the screen was initially demonstrated using avidin-coated beads prebound to biotinylated PtdIns-3,4-P(2) and PtdIns-3,4,5-P(3) to specifically isolate the pleckstrin homology domain of the serine/threonine kinase Akt [17].
  • Second, using a construct lacking this pleckstrin homology domain, which does not require translocation for activation, we found that ceramide stimulates the dephosphorylation of Akt/PKB by protein phosphatase 2A [18].
  • Serum- and glucocorticoid-regulated kinase (SGK) is a serine kinase that has a catalytic domain homologous to that of Akt, but lacks the pleckstrin homology domain present in Akt [19].

Physical interactions of Plek


Regulatory relationships of Plek

  • These results indicate that Akt1 and 3 are similarly stimulated by insulin and this stimulation is inhibited by prior activation of protein kinase C through a mechanism that is independent of the presence of the pleckstrin homology domain [21].
  • Pleckstrin expression in mouse macrophages was induced severalfold in response to bacterial LPS and IFN-gamma [11].

Other interactions of Plek

  • Using several mutant forms of Mtmr2, we identified two domains that are necessary for membrane association: (i) A pleckstrin homology-GRAM domain; and (ii) a coiled-coil module [8].
  • Targeting of Tiam1 to the plasma membrane requires the cooperative function of the N-terminal pleckstrin homology domain and an adjacent protein interaction domain [15].
  • Akt2 encodes a protein-serine/threonine kinase containing a pleckstrin homology domain characteristic of many signaling molecules [22].
  • Since this inhibition could have resulted from an interaction of the pleckstrin homology domain of the Akt with protein kinase C, we also examined the ability of a mutant Akt1 lacking this domain to be regulated by this enzyme [21].
  • The amino-terminal pleckstrin homology (PH) domain of IRS-1 plays a pivotal role in promoting insulin receptor (IR)-IRS-1 protein interactions [23].

Analytical, diagnostic and therapeutic context of Plek


  1. 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]
  2. Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vav. Tarakhovsky, A., Turner, M., Schaal, S., Mee, P.J., Duddy, L.P., Rajewsky, K., Tybulewicz, V.L. Nature (1995) [Pubmed]
  3. Lnk inhibits Tpo-mpl signaling and Tpo-mediated megakaryocytopoiesis. Tong, W., Lodish, H.F. J. Exp. Med. (2004) [Pubmed]
  4. Visualization of IP(3) dynamics reveals a novel AMPA receptor-triggered IP(3) production pathway mediated by voltage-dependent Ca(2+) influx in Purkinje cells. Okubo, Y., Kakizawa, S., Hirose, K., Iino, M. Neuron (2001) [Pubmed]
  5. Localized biphasic changes in phosphatidylinositol-4,5-bisphosphate at sites of phagocytosis. Botelho, R.J., Teruel, M., Dierckman, R., Anderson, R., Wells, A., York, J.D., Meyer, T., Grinstein, S. J. Cell Biol. (2000) [Pubmed]
  6. Visualization of phosphoinositides that bind pleckstrin homology domains: calcium- and agonist-induced dynamic changes and relationship to myo-[3H]inositol-labeled phosphoinositide pools. Várnai, P., Balla, T. J. Cell Biol. (1998) [Pubmed]
  7. Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors. Andjelković, M., Jakubowicz, T., Cron, P., Ming, X.F., Han, J.W., Hemmings, B.A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  8. Membrane association of myotubularin-related protein 2 is mediated by a pleckstrin homology-GRAM domain and a coiled-coil dimerization module. Berger, P., Schaffitzel, C., Berger, I., Ban, N., Suter, U. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  9. Requirement of Gab2 for mast cell development and KitL/c-Kit signaling. Nishida, K., Wang, L., Morii, E., Park, S.J., Narimatsu, M., Itoh, S., Yamasaki, S., Fujishima, M., Ishihara, K., Hibi, M., Kitamura, Y., Hirano, T. Blood (2002) [Pubmed]
  10. The Ras/p120 GTPase-activating protein (GAP) interaction is regulated by the p120 GAP pleckstrin homology domain. Drugan, J.K., Rogers-Graham, K., Gilmer, T., Campbell, S., Clark, G.J. J. Biol. Chem. (2000) [Pubmed]
  11. Expression of the protein kinase C substrate pleckstrin in macrophages: association with phagosomal membranes. Brumell, J.H., Howard, J.C., Craig, K., Grinstein, S., Schreiber, A.D., Tyers, M. J. Immunol. (1999) [Pubmed]
  12. Src-induced activation of inducible T cell kinase (ITK) requires phosphatidylinositol 3-kinase activity and the Pleckstrin homology domain of inducible T cell kinase. August, A., Sadra, A., Dupont, B., Hanafusa, H. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  13. Neutrophils lacking phosphoinositide 3-kinase gamma show loss of directionality during N-formyl-Met-Leu-Phe-induced chemotaxis. Hannigan, M., Zhan, L., Li, Z., Ai, Y., Wu, D., Huang, C.K. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  14. The spatial and temporal dynamics of pleckstrin homology domain binding at the plasma membrane measured by imaging single molecules in live mouse myoblasts. Mashanov, G.I., Tacon, D., Peckham, M., Molloy, J.E. J. Biol. Chem. (2004) [Pubmed]
  15. Targeting of Tiam1 to the plasma membrane requires the cooperative function of the N-terminal pleckstrin homology domain and an adjacent protein interaction domain. Stam, J.C., Sander, E.E., Michiels, F., van Leeuwen, F.N., Kain, H.E., van der Kammen, R.A., Collard, J.G. J. Biol. Chem. (1997) [Pubmed]
  16. Inhibition of the motility and growth of B16F10 mouse melanoma cells by dominant negative mutants of Dok-1. Hosooka, T., Noguchi, T., Nagai, H., Horikawa, T., Matozaki, T., Ichihashi, M., Kasuga, M. Mol. Cell. Biol. (2001) [Pubmed]
  17. Expression cloning of protein targets for 3-phosphorylated phosphoinositides. Rao, V.R., Corradetti, M.N., Chen, J., Peng, J., Yuan, J., Prestwich, G.D., Brugge, J.S. J. Biol. Chem. (1999) [Pubmed]
  18. Regulation of insulin action by ceramide: dual mechanisms linking ceramide accumulation to the inhibition of Akt/protein kinase B. Stratford, S., Hoehn, K.L., Liu, F., Summers, S.A. J. Biol. Chem. (2004) [Pubmed]
  19. Differing roles of Akt and serum- and glucocorticoid-regulated kinase in glucose metabolism, DNA synthesis, and oncogenic activity. Sakoda, H., Gotoh, Y., Katagiri, H., Kurokawa, M., Ono, H., Onishi, Y., Anai, M., Ogihara, T., Fujishiro, M., Fukushima, Y., Abe, M., Shojima, N., Kikuchi, M., Oka, Y., Hirai, H., Asano, T. J. Biol. Chem. (2003) [Pubmed]
  20. Deletion of the pleckstrin and phosphotyrosine binding domains of insulin receptor substrate-2 does not impair its ability to regulate cell proliferation in myeloid cells. Sun, H., Baserga, R. Endocrinology (2004) [Pubmed]
  21. Protein kinase C modulates the insulin-stimulated increase in Akt1 and Akt3 activity in 3T3-L1 adipocytes. Barthel, A., Nakatani, K., Dandekar, A.A., Roth, R.A. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  22. Akt2 mRNA is highly expressed in embryonic brown fat and the AKT2 kinase is activated by insulin. Altomare, D.A., Lyons, G.E., Mitsuuchi, Y., Cheng, J.Q., Testa, J.R. Oncogene (1998) [Pubmed]
  23. The pleckstrin homology (PH) domain-interacting protein couples the insulin receptor substrate 1 PH domain to insulin signaling pathways leading to mitogenesis and GLUT4 translocation. Farhang-Fallah, J., Randhawa, V.K., Nimnual, A., Klip, A., Bar-Sagi, D., Rozakis-Adcock, M. Mol. Cell. Biol. (2002) [Pubmed]
  24. Binding of a Pleckstrin homology domain protein to phosphoinositide in membranes: a miniaturized FRET-based assay for drug screening. Hamman, B.D., Pollok, B.A., Bennett, T., Allen, J., Heim, R. Journal of biomolecular screening : the official journal of the Society for Biomolecular Screening. (2002) [Pubmed]
WikiGenes - Universities