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Mol. Cell. Biol., Mar 1996, 977-989, Vol 16, No. 3
M Mohammadi, I Dikic, A Sorokin, WH Burgess, M Jaye and J Schlessinger
Fibroblast growth factor receptor (FGFR) activation leads to receptor
autophosphorylation and increased tyrosine phosphorylation of several intra
cellular proteins. We have previously shown that autophosphorylated
tyrosine 766 in FGFR1 serves as a binding site for one of the SH2 domains
of phospholipase Cy and couples FGFR1 to phosphatidylinositol hydrolysis in
several cell types. In this report, we describe the identification of six
additional autophosphorylation sites (Y-463, Y-583, Y-585, Y-653, Y-654 and
Y-730) on FGFR1. We demonstrate that autophosphorylation on tyrosines 653
and 654 is important for activation of tyrosine kinase activity of FGFR1
and is therefore essential for FGFR1-mediated biological responses. In
contrast, autophosphorylation of the remaining four tyrosines is
dispensable for FGFR1-mediated mitogen-activated protein kinase activation
and mitogenic signaling in L-6 cells as well as neuronal differentiation of
PC12 cells. Interestingly, both the wild-type and a mutant FGFR1 (FGFR1-4F)
are able to phosphorylate Shc and an unidentified Grb2-associated
phosphoprotein of 90 kDa (pp90). Binding of the Grb2/Sos complex to
phosphorylated Shc and pp90 may therefore be the key link between FGFR1 and
the Ras signaling pathway, mito-genesis, and neuronal differentiation.
Copyright © 1996, American Society for Microbiology
Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction
Department of Pharmacology, New York University Medical Center, 10016, USA.
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