7z75

Structural highlights

Function

[P3C2A_MOUSE] Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin-mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin-independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function.^{[1] [2] [3]}

References

1. ↑ Virbasius JV, Guilherme A, Czech MP. Mouse p170 is a novel phosphatidylinositol 3-kinase containing a C2 domain. J Biol Chem. 1996 Jun 7;271(23):13304-7. PMID:8663140
2. ↑ Leibiger B, Moede T, Uhles S, Barker CJ, Creveaux M, Domin J, Berggren PO, Leibiger IB. Insulin-feedback via PI3K-C2alpha activated PKBalpha/Akt1 is required for glucose-stimulated insulin secretion. FASEB J. 2010 Jun;24(6):1824-37. doi: 10.1096/fj.09-148072. Epub 2010 Jan 8. PMID:20061534 doi:http://dx.doi.org/10.1096/fj.09-148072
3. ↑ Harris DP, Vogel P, Wims M, Moberg K, Humphries J, Jhaver KG, DaCosta CM, Shadoan MK, Xu N, Hansen GM, Balakrishnan S, Domin J, Powell DR, Oravecz T. Requirement for class II phosphoinositide 3-kinase C2alpha in maintenance of glomerular structure and function. Mol Cell Biol. 2011 Jan;31(1):63-80. doi: 10.1128/MCB.00468-10. Epub 2010 Oct 25. PMID:20974805 doi:http://dx.doi.org/10.1128/MCB.00468-10