The atypical Rho GTPase Wrch1 collaborates with the nonreceptor tyrosine kinases Pyk2 and Src in regulating cytoskeletal dynamics
2008 (English)In: Molecular and Cellular Biology, ISSN 0270-7306, Vol. 28, no 5, 1802-14 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2008. Vol. 28, no 5, 1802-14 p.
Wrch1, Rho GTPase, Pyk2, FAK, focal adhesion
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-12868DOI: 10.1128/MCB.00201-07ISI: 000253603100032PubMedID: 18086875OAI: oai:DiVA.org:uu-12868DiVA: diva2:40638