| First Author | Keilhack H | Year | 2001 |
| Journal | J Cell Biol | Volume | 152 |
| Issue | 2 | Pages | 325-34 |
| PubMed ID | 11266449 | Mgi Jnum | J:67582 |
| Mgi Id | MGI:1930880 | Doi | 10.1083/jcb.152.2.325 |
| Citation | Keilhack H, et al. (2001) Negative Regulation of Ros Receptor Tyrosine Kinase Signaling. An epithelial function of the sh2 domain protein tyrosine phosphatase shp-1. J Cell Biol 152(2):325-34 |
| abstractText | 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 NH(2)-terminal SH2 domain and Ros phosphotyrosine 2267. Overexpression of SHP-1 results in Ros dephosphorylation and effectively downregulates Ros-dependent proliferation and transformation. We propose that SHP-1 is an important downstream regulator of Ros signaling. |
