Publication: Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation
Issued Date
2016-10-01
Resource Type
ISSN
18733913
08986568
08986568
Other identifier(s)
2-s2.0-84989837159
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cellular Signalling. Vol.28, No.10 (2016), 1580-1592
Suggested Citation
Lewis J. Watson, Kevin M. Alexander, Maradumane L. Mohan, Amber L. Bowman, Supachoke Mangmool, Kunhong Xiao, Sathyamangla V. Naga Prasad, Howard A. Rockman Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation. Cellular Signalling. Vol.28, No.10 (2016), 1580-1592. doi:10.1016/j.cellsig.2016.05.006 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/42931
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation
Abstract
© 2016 Elsevier Inc. β2-Adrenergic receptors (β2AR) transactivate epidermal growth factor receptors (EGFR) through formation of a β2AR–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 β2AR-stimulated EGFR transactivation. Mechanistically, the generation of phosphatidylinositol (3,4,5)-tris-phosphate (PIP3) by the lipid kinase function stabilizes β2AR–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 βAR 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.