Inhibition of basal FGF receptor signaling by dimeric Grb2

Chi Chuan Lin, Fernando A. Melo, Ragini Ghosh, Kin M. Suen, Loren J. Stagg, John Kirkpatrick, Stefan Arold, Zamal Ahmed, John E. Ladbury*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Receptor tyrosine kinase activity is known to occur in the absence of extracellular stimuli. Importantly, this "background" level of receptor phosphorylation is insufficient to effect a downstream response, suggesting that strict controls are present and prohibit full activation. Here a mechanism is described in which control of FGFR2 activation is provided by the adaptor protein Grb2. Dimeric Grb2 binds to the C termini of two FGFR2 molecules. This heterotetramer is capable of a low-level receptor transphosphorylation, but C-terminal phosphorylation and recruitment of signaling proteins are sterically hindered. Upon stimulation, FGFR2 phosphorylates tyrosine residues on Grb2, promoting dissociation from the receptor and allowing full activation of downstream signaling. These observations establish a role for Grb2 as an active regulator of RTK signaling.

Original languageEnglish (US)
Pages (from-to)1514-1524
Number of pages11
JournalCell
Volume149
Issue number7
DOIs
StatePublished - Jun 22 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'Inhibition of basal FGF receptor signaling by dimeric Grb2'. Together they form a unique fingerprint.

Cite this