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Gene Review

PIK3C2B  -  phosphatidylinositol-4-phosphate 3-kinase,...

Homo sapiens

Synonyms: C2-PI3K, PI3K-C2-beta, PI3K-C2beta, Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta, Phosphoinositide 3-kinase-C2-beta, ...
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High impact information on PIK3C2B

  • Both PtdIns-3-P and PI3K-C2beta are involved in LPA-mediated cell migration [1].
  • This study is the first identification of PtdIns-3-P and PI3K-C2beta as downstream effectors in LPA signaling and demonstration of an intracellular role for a class II PI3K [1].
  • Since these findings revealed that the interaction between the EGF receptor and PI3K-C2beta is indirect, we sought to identify an adaptor molecule that could mediate their association [2].
  • Recombinant Grb2 directly bound PI3K-C2beta in vitro, and this effect was reproduced using either SH3 domain expressed as a glutathione S-transferase (GST) fusion [2].
  • Previously we demonstrated that the class II phosphoinositide 3-kinase C2beta (PI3K-C2beta) is rapidly recruited to a phosphotyrosine signaling complex containing the activated receptor for epidermal growth factor (EGF) [2].

Biological context of PIK3C2B


Anatomical context of PIK3C2B

  • The relevance of this association was confirmed when PI3K-C2beta was isolated by coimmunoprecipitation with anti-Grb2 antibody from numerous cell lines [2].
  • EGF and platelet-derived growth factor also stimulated the association of PI3K-C2beta with their respective receptors in other cells, including epithelial cells and fibroblasts [6].
  • Using asynchronous cultures, we show that endogenous PI3K-C2beta is present in lamellipodia of motile cells [4].
  • Overexpression of a 2xFYVE(Hrs) domain fusion protein abolished this response demonstrating that the effect of PI3K-C2beta on the reorganization of actin filaments is dependent upon PtdIns3P [4].
  • Our data demonstrates for the first time, that PI3K-C2beta plays a regulatory role in cell motility and that the mechanism by which it reorganizes the actin cytoskeleton is dependent upon PtdIns3P production [4].

Associations of PIK3C2B with chemical compounds


Physical interactions of PIK3C2B

  • The N-terminal region of PI3K-C2beta was found to selectively interact with the EGF receptor in vitro, suggesting that it mediates the association of this PI3K with the receptor [6].

Regulatory relationships of PIK3C2B


Other interactions of PIK3C2B

  • Further, a series of N-terminal PI3K-C2beta fragments, truncated prior to each proline-rich region, bound the receptor with decreased efficiency [2].
  • Ligand addition also induced the appearance of a second, more slowly migrating band of PI3K-C2alpha and PI3K-C2beta immunoreactivity on sodium dodecyl sulfate-polyacrylamide gel electrophoresis [6].
  • When cells expressing recombinant PI3K-C2beta were plated onto fibronectin, cortical actin staining increased markedly and actin rich lamellipodia and filopodia became evident [4].
  • Finally, overexpression of PI3K-C2beta increased GTP loading of Cdc42 [4].

Analytical, diagnostic and therapeutic context of PIK3C2B


  1. Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration. Maffucci, T., Cooke, F.T., Foster, F.M., Traer, C.J., Fry, M.J., Falasca, M. J. Cell Biol. (2005) [Pubmed]
  2. Recruitment of the class II phosphoinositide 3-kinase C2beta to the epidermal growth factor receptor: role of Grb2. Wheeler, M., Domin, J. Mol. Cell. Biol. (2001) [Pubmed]
  3. Human phosphoinositide 3-kinase C2beta, the role of calcium and the C2 domain in enzyme activity. Arcaro, A., Volinia, S., Zvelebil, M.J., Stein, R., Watton, S.J., Layton, M.J., Gout, I., Ahmadi, K., Downward, J., Waterfield, M.D. J. Biol. Chem. (1998) [Pubmed]
  4. The class II phosphoinositide 3-kinase PI3K-C2beta regulates cell migration by a PtdIns3P dependent mechanism. Domin, J., Harper, L., Aubyn, D., Wheeler, M., Florey, O., Haskard, D., Yuan, M., Zicha, D. J. Cell. Physiol. (2005) [Pubmed]
  5. Nuclear phosphoinositide 3-kinase C2beta activation during G2/M phase of the cell cycle in HL-60 cells. Visnjić, D., Curić, J., Crljen, V., Batinić, D., Volinia, S., Banfić, H. Biochim. Biophys. Acta (2003) [Pubmed]
  6. Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors. Arcaro, A., Zvelebil, M.J., Wallasch, C., Ullrich, A., Waterfield, M.D., Domin, J. Mol. Cell. Biol. (2000) [Pubmed]
  7. The activation of nuclear phosphoinositide 3-kinase C2beta in all-trans-retinoic acid-differentiated HL-60 cells. Visnjić, D., Crljen, V., Curić, J., Batinić, D., Volinia, S., Banfić, H. FEBS Lett. (2002) [Pubmed]
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