Work

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

Year: 2014

Type: article

Abstract: 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 [IP(3)] and diacylglycerol. IP(3) thus formed can be further converted to inositol (1,3,4,5)-tetrakisphosphate [IP(4)] by an enzyme called IP(3)-kinase [IP(3)K]. In this study we have investigated the effect of modulation of intracellular IP(3)K activity by the use of an inhibitor, 2-trifluoromethyl [6-(4-nitrobenzyl)-purine] [IP(3)KI] and siRNA against IP(3)KB 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 IP(3)KI and siRNA against IP(3)KB. Inhibition of ERK-phosphorylation was accompanied by decreased cell migration in the presence of IP(3)KI.

Source: Journal of Pharmaceutical Sciences and Pharmacology

DOI: 10.1166/jpsp.2014.1010

Authors: M. C. Sekar, K. Shahiwala, L. Leloup, A. Wells

Institutions: University of Findlay, University of Pittsburgh

Language: English

Topic: Protein Kinase Regulation and GTPase Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Awards: Spatial Segregation of Cell Functioning during Motility, Dermal-Epidermal Communication during Wound Healing