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

Publication ,  Journal Article
Watson, LJ; Alexander, KM; Mohan, ML; Bowman, AL; Mangmool, S; Xiao, K; Naga Prasad, SV; Rockman, HA
Published in: Cell Signal
October 2016

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.

Duke Scholars

Published In

Cell Signal

DOI

EISSN

1873-3913

Publication Date

October 2016

Volume

28

Issue

10

Start / End Page

1580 / 1592

Location

England

Related Subject Headings

  • src-Family Kinases
  • Transcriptional Activation
  • Proto-Oncogene Proteins c-akt
  • Phosphoserine
  • Phosphorylation
  • Phosphatidylinositol 3-Kinases
  • Models, Biological
  • Mass Spectrometry
  • Isoproterenol
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Watson, L. J., Alexander, K. M., Mohan, M. L., Bowman, A. L., Mangmool, S., Xiao, K., … Rockman, H. A. (2016). Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation. Cell Signal, 28(10), 1580–1592. https://doi.org/10.1016/j.cellsig.2016.05.006
Watson, Lewis J., Kevin M. Alexander, Maradumane L. Mohan, Amber L. Bowman, Supachoke Mangmool, Kunhong Xiao, Sathyamangla V. Naga Prasad, and Howard A. Rockman. “Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation.Cell Signal 28, no. 10 (October 2016): 1580–92. https://doi.org/10.1016/j.cellsig.2016.05.006.
Watson LJ, Alexander KM, Mohan ML, Bowman AL, Mangmool S, Xiao K, et al. Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation. Cell Signal. 2016 Oct;28(10):1580–92.
Watson, Lewis J., et al. “Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation.Cell Signal, vol. 28, no. 10, Oct. 2016, pp. 1580–92. Pubmed, doi:10.1016/j.cellsig.2016.05.006.
Watson LJ, Alexander KM, Mohan ML, Bowman AL, Mangmool S, Xiao K, Naga Prasad SV, Rockman HA. Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation. Cell Signal. 2016 Oct;28(10):1580–1592.
Journal cover image

Published In

Cell Signal

DOI

EISSN

1873-3913

Publication Date

October 2016

Volume

28

Issue

10

Start / End Page

1580 / 1592

Location

England

Related Subject Headings

  • src-Family Kinases
  • Transcriptional Activation
  • Proto-Oncogene Proteins c-akt
  • Phosphoserine
  • Phosphorylation
  • Phosphatidylinositol 3-Kinases
  • Models, Biological
  • Mass Spectrometry
  • Isoproterenol
  • Humans