The protein tyrosine phosphatase Shp-2 regulates RhoA activity

Simone M. Schoenwaelder, Leslie A. Petch, David Williamson, Randy Shen, Gen Sheng Feng, Keith Burridge

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

Remodeling of filamentous actin into distinct arrangements is precisely controlled by members of the Rho family of small GTPases [1]. A well characterized member of this family is RhoA, whose activation results in reorganization of the cytoskeleton into thick actin stress fibers terminating in Integrin-rich focal adhesions [2]. Regulation of RhoA is required to maintain adhesion in stationary cells, but is also critical for cell spreading and migration [3]. Despite its biological importance, the signaling events leading to RhoA activation are not fully understood. Several independent studies have implicated tyrosine phosphorylation as a critical event upstream of RhoA [4]. Consistent with this, our recent studies have demonstrated the existence of a protein tyrosine phosphatase (PTPase), sensitive to the dipeptide aldehyde calpeptin, acting upstream of RhoA [5]. Here we identify the SH2 (Src homology region 2)-containing PTPase Shp-2 as a calpeptin-sensitive PTPase, and show that calpeptin interferes with the catalytic activity of Shp-2 in vitro and with Shp-2 signaling in vivo. Finally, we show that perturbation of Shp-2 activity by a variety of genetic manipulations results in raised levels of active RhoA. Together, these studies identify Shp-2 as a PTPase acting upstream of RhoA to regulate its activity and contribute to the coordinated control of cell movement.

Original languageEnglish (US)
Pages (from-to)1523-1526
Number of pages4
JournalCurrent Biology
Volume10
Issue number23
DOIs
StatePublished - Nov 30 2000

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Schoenwaelder, S. M., Petch, L. A., Williamson, D., Shen, R., Feng, G. S., & Burridge, K. (2000). The protein tyrosine phosphatase Shp-2 regulates RhoA activity. Current Biology, 10(23), 1523-1526. https://doi.org/10.1016/S0960-9822(00)00831-9