PIK3C2B explained

Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing beta polypeptide is an enzyme that in humans is encoded by the PIK3C2B gene.^{[1] [2] [3]}

Function

The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is sensitive to low nanomolar levels of the inhibitor wortmannin. The C2 domain of this protein was shown to bind phospholipids but not Ca²⁺, which suggests that this enzyme may function in a calcium-independent manner.

Further reading

• Lee C, Liu QH, Tomkowicz B, Yi Y, Freedman BD, Collman RG . Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways . Journal of Leukocyte Biology . 74 . 5 . 676–82 . Nov 2003 . 12960231 . 10.1189/jlb.0503206 . 11362623 .
• Kozutsumi H, Toyoshima H, Hagiwara K, Yazaki Y, Hirai H . Human ltk receptor tyrosine kinase binds to PLC-gamma 1, PI3-K, GAP and Raf-1 in vivo . Oncogene . 9 . 10 . 2991–8 . Oct 1994 . 8084603 .
• Milani D, Mazzoni M, Borgatti P, Zauli G, Cantley L, Capitani S . Extracellular human immunodeficiency virus type-1 Tat protein activates phosphatidylinositol 3-kinase in PC12 neuronal cells . The Journal of Biological Chemistry . 271 . 38 . 22961–4 . Sep 1996 . 8798481 . 10.1074/jbc.271.38.22961 . free .
• Ueno H, Honda H, Nakamoto T, Yamagata T, Sasaki K, Miyagawa K, Mitani K, Yazaki Y, Hirai H . The phosphatidylinositol 3' kinase pathway is required for the survival signal of leukocyte tyrosine kinase . Oncogene . 14 . 25 . 3067–72 . Jun 1997 . 9223670 . 10.1038/sj.onc.1201153 . free .
• Mazerolles F, Barbat C, Fischer A . Down-regulation of LFA-1-mediated T cell adhesion induced by the HIV envelope glycoprotein gp160 requires phosphatidylinositol-3-kinase activity . European Journal of Immunology . 27 . 9 . 2457–65 . Sep 1997 . 9341793 . 10.1002/eji.1830270946 . 33397908 .
• Borgatti P, Zauli G, Colamussi ML, Gibellini D, Previati M, Cantley LL, Capitani S . Extracellular HIV-1 Tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4+ T lymphoblastoid Jurkat cells . European Journal of Immunology . 27 . 11 . 2805–11 . Nov 1997 . 9394803 . 10.1002/eji.1830271110 . 6303471 .
• Borgatti P, Zauli G, Cantley LC, Capitani S . Extracellular HIV-1 Tat protein induces a rapid and selective activation of protein kinase C (PKC)-alpha, and -epsilon and -zeta isoforms in PC12 cells . Biochemical and Biophysical Research Communications . 242 . 2 . 332–7 . Jan 1998 . 9446795 . 10.1006/bbrc.1997.7877 .
• Milani D, Mazzoni M, Zauli G, Mischiati C, Gibellini D, Giacca M, Capitani S . HIV-1 Tat induces tyrosine phosphorylation of p125FAK and its association with phosphoinositide 3-kinase in PC12 cells . AIDS . 12 . 11 . 1275–84 . Jul 1998 . 9708406 . 10.1097/00002030-199811000-00008 . 25758704 . free .
• Jauliac S, Mazerolles F, Jabado N, Pallier A, Bernard F, Peake J, Fischer A, Hivroz C . Ligands of CD4 inhibit the association of phospholipase Cgamma1 with phosphoinositide 3 kinase in T cells: regulation of this association by the phosphoinositide 3 kinase activity . European Journal of Immunology . 28 . 10 . 3183–91 . Oct 1998 . 9808187 . 10.1002/(SICI)1521-4141(199810)28:10<3183::AID-IMMU3183>3.0.CO;2-A . free .
• Arcaro A, Zvelebil MJ, Wallasch C, Ullrich A, Waterfield MD, Domin J . Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors . Molecular and Cellular Biology . 20 . 11 . 3817–30 . Jun 2000 . 10805725 . 85707 . 10.1128/MCB.20.11.3817-3830.2000 .
• Park IW, Wang JF, Groopman JE . HIV-1 Tat promotes monocyte chemoattractant protein-1 secretion followed by transmigration of monocytes . Blood . 97 . 2 . 352–8 . Jan 2001 . 11154208 . 10.1182/blood.V97.2.352 . free .
• Zauli G, Milani D, Mirandola P, Mazzoni M, Secchiero P, Miscia S, Capitani S . HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway . FASEB Journal . 15 . 2 . 483–91 . Feb 2001 . 11156964 . 10.1096/fj.00-0354com . free . 26315564 .
• Wheeler M, Domin J . Recruitment of the class II phosphoinositide 3-kinase C2beta to the epidermal growth factor receptor: role of Grb2 . Molecular and Cellular Biology . 21 . 19 . 6660–7 . Oct 2001 . 11533253 . 99811 . 10.1128/MCB.21.19.6660-6667.2001 .
• Deregibus MC, Cantaluppi V, Doublier S, Brizzi MF, Deambrosis I, Albini A, Camussi G . HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival pathways in Kaposi's sarcoma cells . The Journal of Biological Chemistry . 277 . 28 . 25195–202 . Jul 2002 . 11994280 . 10.1074/jbc.M200921200 . free .
• Cook JA, August A, Henderson AJ . Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by a Tat-dependent mechanism . Journal of Immunology . 169 . 1 . 254–60 . Jul 2002 . 12077252 . 10.4049/jimmunol.169.1.254 . free .
• Arcaro A, Khanzada UK, Vanhaesebroeck B, Tetley TD, Waterfield MD, Seckl MJ . Two distinct phosphoinositide 3-kinases mediate polypeptide growth factor-stimulated PKB activation . The EMBO Journal . 21 . 19 . 5097–108 . Oct 2002 . 12356726 . 129034 . 10.1093/emboj/cdf512 .
• Visnjić D, Crljen V, Curić J, Batinić D, Volinia S, Banfić H . The activation of nuclear phosphoinositide 3-kinase C2beta in all-trans-retinoic acid-differentiated HL-60 cells . FEBS Letters . 529 . 2–3 . 268–74 . Oct 2002 . 12372612 . 10.1016/S0014-5793(02)03357-4 . 29067083 .

Notes and References

1. Brown RA, Ho LK, Weber-Hall SJ, Shipley JM, Fry MJ . Identification and cDNA cloning of a novel mammalian C2 domain-containing phosphoinositide 3-kinase, HsC2-PI3K . Biochemical and Biophysical Research Communications . 233 . 2 . 537–44 . Apr 1997 . 9144573 . 10.1006/bbrc.1997.6495 .
2. Arcaro A, Volinia S, Zvelebil MJ, Stein R, Watton SJ, Layton MJ, Gout I, Ahmadi K, Downward J, Waterfield MD . Human phosphoinositide 3-kinase C2beta, the role of calcium and the C2 domain in enzyme activity . The Journal of Biological Chemistry . 273 . 49 . 33082–90 . Dec 1998 . 9830063 . 10.1074/jbc.273.49.33082 . free .
3. Web site: Entrez Gene: PIK3C2B phosphoinositide-3-kinase, class 2, beta polypeptide.