Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction. Mol Cell Biol 1996 Mar;16(3):977-89
Date
03/01/1996Pubmed ID
8622701Pubmed Central ID
PMC231080DOI
10.1128/MCB.16.3.977Scopus ID
2-s2.0-0030027488 (requires institutional sign-in at Scopus site) 355 CitationsAbstract
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.
Author List
Mohammadi M, Dikic I, Sorokin A, Burgess WH, Jaye M, Schlessinger JAuthor
Andrey Sorokin PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Base Sequence
Cell Differentiation
Cell Line
Mice
Molecular Sequence Data
Neurons
Phosphorylation
Receptor Protein-Tyrosine Kinases
Receptor, Fibroblast Growth Factor, Type 1
Receptors, Fibroblast Growth Factor
Sequence Analysis
Signal Transduction
