Novel recruitment of Shc, Grb2, and Sos by fibroblast growth factor receptor-1 in v-Src-transformed cells

Area of Science:

• Cellular signaling pathways
• Receptor tyrosine kinases
• Oncogene signaling

Background:

• Fibroblast growth factor receptor-1 (FGFR-1) normally associates with phospholipase C gamma (PLC gamma) upon tyrosine phosphorylation induced by fibroblast growth factor (FGF).
• The viral Src (v-Src) oncoprotein is known to induce tyrosine phosphorylation of various cellular proteins, including FGFR-1.

Purpose of the Study:

• To investigate the downstream signaling events following v-Src-induced tyrosine phosphorylation of FGFR-1.
• To determine if v-Src-transformed cells utilize the same FGFR-1 signaling pathway as FGF-stimulated cells.

Main Methods:

• Western blotting to detect tyrosine phosphorylation of FGFR-1.
• Co-immunoprecipitation assays to identify proteins associated with tyrosine-phosphorylated FGFR-1 in v-Src-transformed cells and FGF-stimulated cells.
• Treatment with suramin to investigate the mechanism of association.

Main Results:

• In v-Src-transformed cells, FGFR-1 undergoes tyrosine phosphorylation but does not associate with PLC gamma or p90.
• Instead, tyrosine-phosphorylated FGFR-1 constitutively associates with Shc, Grb2, and Sos, key components of the Ras signaling pathway.
• This Shc/Grb2/Sos complex association is not observed in response to FGF and is not inhibited by suramin, suggesting a non-autocrine mechanism.

Conclusions:

• v-Src transforms FGFR-1 signaling by recruiting the Ras-activating Shc/Grb2/Sos complex, distinct from the canonical FGF-induced PLC gamma pathway.
• These findings propose a novel mechanism for Ras activation by v-Src through the phosphorylation of previously unidentified tyrosine residues on FGFR-1.