Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 277, Issue 18, Pages 15962-15970Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M102777200
Keywords
-
Categories
Funding
- NIDCR NIH HHS [1R01 DE12581] Funding Source: Medline
Ask authors/readers for more resources
Fibroblast growth factor receptor 3 (FGFR3) influences a diverse array of biological processes, including cell growth, differentiation, and migration. Activating mutations in FGFR3 are associated with multiple myeloma, cervical carcinoma, and bladder cancer. To identify proteins that interact with FGFR3 and which may mediate FGFR3-dependent signaling, a yeast two-hybrid screen was employed using the cytoplasmic kinase domain of FGFR3 as bait. We identified the adapter protein SH2-B as an FGFR3-interacting protein. Coimmunoprecipitation experiments demonstrate binding of the SH2-Bbeta isoform to FGFR3 in 293T cells. Tyrosine phosphorylation of SH2-Bbeta was observed when coexpressed with activated FGFR3 mutants such as the weakly activated mutant N540K or the strongly activated mutant K650E, both associated with human developmental syndromes. The extent of tyrosine phosphorylation of SH2-Bbeta correlates with receptor activation, suggesting that FGFR3 activation mediates tyrosine phosphorylation of SH2-Bbeta. Furthermore, two tyrosine phosphorylation sites of FGFR3, Tyr-724 and Tyr-760, are required for optimal binding of the Src homology-2 (SH2) domain of SH2-Bbeta We also demonstrate the phosphorylation and nuclear translocation of Stat5 by activated FGFR3, which increases in response to overexpression of SH2-Bbeta. Taken together, our results identify SH2-Bbeta as a novel FGFR,3 binding partner that mediates signal transduction.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available