Modulation of Epidermal Growth Factor Stimulated ERK Phosphorylation and Cell Motility by Inositol Trisphosphate Kinase.

Epidermal growth factor [EGF] mediated stimulation of its receptor in endothelial cell [EC] is accompanied by phosphorylation of the EGF-receptor [EGFR] and activation of phospholipase C-γ, resulting in the breakdown of phosphatidylinositol(4,5)-bisphosphate and generating inositol (1,4,5)-trisphosphate [IP3] and diacylglycerol. IP3 thus formed can be further converted to inositol (1,3,4,5)-tetrakisphosphate [IP4] by an enzyme called IP3-kinase [IP3K]. In this study we have investigated the effect of modulation of intracellular IP3K activity by the use of an inhibitor, 2-trifluoromethyl [6-(4-nitrobenzyl)-purine] [IP3KI] and siRNA against IP3KB on EGF-induced ERK-phosphorylation and cell motility. EGF stimulated ERK-phosphorylation that has been implicated in EGF-stimulated cell migration was inhibited by both IP3KI and siRNA against IP3KB. Inhibition of ERK-phosphorylation was accompanied by decreased cell migration in the presence of IP3KI.