Journal
JOURNAL OF CELL BIOLOGY
Volume 152, Issue 2, Pages 325-334Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.152.2.325
Keywords
protein tyrosine phosphatase; regulation; receptor tyrosine kinase; epididymis; fertility
Categories
Ask authors/readers for more resources
Male viable motheaten (me(v)) mice, with a naturally occurring mutation in the gene of the SH2 domain protein tyrosine phosphatase SHP-1, are sterile. Known defects in sperm maturation in these mice correlate with an impaired differentiation of the epididymis, which has similarities to the phenotype of mice with a targeted inactivation of the Ros receptor tyrosine kinase. Ros and SHP-1 are coexpressed in epididymal epithelium, and elevated phosphorylation of Ros in the epididymis of me(v) mice suggests that Ros signaling is under control of SHP-1 in vivo. Phosphorylated Ros strongly and directly associates with SHP-1 in yeast two-hybrid, glutathione S-transferase pull-down, and coimmunoprecipitation experiments. Strong binding of SHP-1 to Ros is selective compared to six other receptor tyrosine kinases, The interaction is mediated by the SHP-1 NH2-terminal SH2 domain and Ros phosphotyrosine 2267. Overexpression of SHP-1 results in Ros dephosphorylation and effectively downregulates Res-dependent proliferation and transformation. We propose that SHP-1 is an important downstream regulator of Ros signaling.
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