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Description

PI(4,5)P2 (PIP2) is synthesized mainly by the phosphorylation of PI by PI 4- kinases that produce phosphatidylinositol 4-phosphate (PI4P), which is then phosphorylated by PI4P 5-kinase (PIP5K). Some PIP2 can also be generated through dephosphorylation of PI(3,4,5)P3 by PTEN. Phosphoryl transfer to positions 4 and 5 in PIP2 requires ATP and the cofactor Mg2+. Although most protein kinases achieve maximal active state at low-micromolar intracellular concentrations of ATP, lipid kinases generally require much higher concentrations of ATP to support their activity. Following its synthesis, PIP2 modulates the functions of various proteins including actin-regulating proteins and ion channels. It also serves as a substrate for phospholipase C (PLC) and a source for second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) that are involved in activation and membrane localization of protein kinase C and in the modulation of ion channel activity in endothelial cells and smooth muscle cells. G-protein (Gq) activation that can result in rapid activation of PLC, can reduce PIP2 levels in cells within seconds. The hydrolysis of PIP2 is shown to be enhanced in cells transformed by oncogenes and tumor viruses. Clone KT10 binds to PIP2 even at picogram levels, however, it does not react with PIP or PI even at microgram levels. It is shown to inhibit the proliferation of Src- and erbB-transformed cells but do not affect the proliferation of untransformed cells. It is also reported to abolish PDGF-induced mitogenesis in both untransformed and ras-transformed cells but does not affect the basal level of mitogenesis. (Ref.: Yoneda, A., et al. (2020). Biochem. Biophys. Res. Commun. 527(4), 1050-1056, Harraz, OF., et al. (2020). Proc. Natl. Acad. Sci. USA. 117(34), 20378-20389, Fukami, K., et al. (1988). Proc. Natl. Acad. Sci. USA. 85(23), 9057-9061).