Negative regulation of Ros receptor tyrosine kinase signaling: An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1

Keilhack, H.; Mueller, M.; Boehmer, S.A.; Frank, C.; Weidner, K.M.; Birchmeier, W.; Ligensa, T.; Berndt, A.; Kosmehl, H.; Gunther, B.; Mueller, T.; Birchmeier, C.; Boehmer, F.D.

Negative regulation of Ros receptor tyrosine kinase signaling: An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1

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Item Type:	Article
Title:	Negative regulation of Ros receptor tyrosine kinase signaling: An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1
Creators Name:	Keilhack, H., Mueller, M., Boehmer, S.A., Frank, C., Weidner, K.M., Birchmeier, W., Ligensa, T., Berndt, A., Kosmehl, H., Gunther, B., Mueller, T., Birchmeier, C. and Boehmer, F.D.
Abstract:	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.
Keywords:	Protein Tyrosine Phosphatase, Regulation, Receptor Tyrosine Kinase, Epididymis, Fertility, Animals, Mice
Source:	Journal of Cell Biology
ISSN:	0021-9525
Publisher:	Rockefeller University Press
Volume:	152
Number:	2
Page Range:	325-334
Date:	22 January 2001
Additional Information:	Copyright (c) 2001 by The Rockefeller University Press
Official Publication:	https://doi.org/10.1083/jcb.152.2.325
PubMed:	View item in PubMed

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