This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.00201-07v1 28/5/1802    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ruusala, A. Articles by Aspenström, P. Search for Related Content PubMed PubMed Citation Articles by Ruusala, A. Articles by Aspenström, P.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2008, p. 1802-1814, Vol. 28, No. 5
0270-7306/08/$08.00+0     doi:10.1128/MCB.00201-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Atypical Rho GTPase Wrch1 Collaborates with the Nonreceptor Tyrosine Kinases Pyk2 and Src in Regulating Cytoskeletal Dynamics

Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, SE-751 24 Uppsala, Sweden

Received 2 February 2007/ Returned for modification 27 July 2007/ Accepted 4 December 2007

The Cdc42-like GTPase Wnt responsive Cdc42 homolog 1 (Wrch1) has several atypical features; it has an N-terminal proline-rich extension that confers binding to SH3 domains, and it harbors an extremely high intrinsic nucleotide exchange activity, which overrides the normal GTPase activity. As a result, Wrch1 resides mainly in the active, GTP-loaded conformation under normal cellular conditions. We have previously shown that ectopic expression of Wrch1 in fibroblasts resulted in an altered cell morphology visible as a formation of filopodia, a loss of stress fibers, and a reduction in focal adhesions. Here, we show that Wrch1 binds to the nonreceptor tyrosine kinase Pyk2. The interaction required Wrch1 to be in a GTP conformation and also required an intact N-terminal proline-rich extension as well as an intact effector loop. Wrch1 requires Pyk2 in imposing the cytoskeletal effects, seen as the formation of filopodia, since treatment of cells with a Pyk2-specific small interfering RNA abrogated this response. Interestingly, we found that the presence and activity of Src were needed for the formation of a Wrch1-Pyk2 complex as well as for the Wrch1-induced formation of filopodia. We propose a model in which Pyk2 and Src function to coordinate the Wrch1-dependent effects on cytoskeletal dynamics.

Published ahead of print on 17 December 2007.