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Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation. Cellular signalling Watson, L. J., Alexander, K. M., Mohan, M. L., Bowman, A. L., Mangmool, S., Xiao, K., Naga Prasad, S. V., Rockman, H. A. 2016; 28 (10): 1580-1592

Abstract

ß2-Adrenergic receptors (ß2AR) transactivate epidermal growth factor receptors (EGFR) through formation of a ß2AR-EGFR complex that requires activation of Src to mediate signaling. Here, we show that both lipid and protein kinase activities of the bifunctional phosphoinositide 3-kinase (PI3K) enzyme are required for ß2AR-stimulated EGFR transactivation. Mechanistically, the generation of phosphatidylinositol (3,4,5)-tris-phosphate (PIP3) by the lipid kinase function stabilizes ß2AR-EGFR complexes while the protein kinase activity of PI3K regulates Src activation by direct phosphorylation. The protein kinase activity of PI3K phosphorylates serine residue 70 on Src to enhance its activity and induce EGFR transactivation following ßAR stimulation. This newly identified function for PI3K, whereby Src is a substrate for the protein kinase activity of PI3K, is of importance since Src plays a key role in pathological and physiological signaling.

View details for DOI 10.1016/j.cellsig.2016.05.006

View details for PubMedID 27169346

View details for PubMedCentralID PMC4980165