Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Watson, LJ; Alexander, KM; Mohan, ML; Bowman, AL; Mangmool, S; Xiao, K; Naga Prasad, SV; Rockman, HA

Published Date

  • October 2016

Published In

Volume / Issue

  • 28 / 10

Start / End Page

  • 1580 - 1592

PubMed ID

  • 27169346

Pubmed Central ID

  • PMC4980165

Electronic International Standard Serial Number (EISSN)

  • 1873-3913

Digital Object Identifier (DOI)

  • 10.1016/j.cellsig.2016.05.006


  • eng

Conference Location

  • England