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Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells

Sells, Mary Ann, Knaus, Ulla G, Bagrodia, Shubha, Ambrose, Diane M, Bokoch, Gary M, Chernoff, Jonathan·1997·Current Biology
DOI 10.1016/s0960-9822(97)70091-5
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Abstract

Background The Rho family GTPases Cdc42, Rac1 and RhoA regulate the reorganization of the actin cytoskeleton induced by extracellular signals such as growth factors. In mammalian cells, Cdc42 regulates the formation of filopodia, whereas Rac regulates lamellipodia formation and membrane ruffling, and RhoA regulates the formation of stress fibers. Recently, the serine/threonine protein kinase p65(pak) autophosphorylates, thereby increasing its catalytic activity towards exogenous substrates. This kinase is therefore a candidate effector for the changes in cell shape induced by growth factors. Results Here, we report that the microinjection of activated Pak1 protein into quiescent Swiss 3T3 cells induces the rapid formation of polarized filopodia and membrane ruffles. The prolonged overexpression of Pak1 amino-terminal mutants that are unable to bind Cdc42 or Rac1 results in the accumulation of filamentous actin in large, polarized membrane ruffles and the formation of vinculin-containing focal complexes within these structures. This phenotype resembles that seen in motile fibroblasts. The amino-terminal Pak1 mutant displays enhanced binding to the adaptor protein Nck, which contains three Src-homology 3 (SH3) domains. Mutation of a proline residue within a conserved SH3-binding region at the amino terminus of Pak1 interferes with SH3-protein binding and alters the effects of Pak1 on the cytoskeleton. Conclusions These results indicate that Pak1, acting through a protein that c…

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Cited by

Metadata

Authors
Sells, M. A., Knaus, U. G., Bagrodia, S., Ambrose, D. M., Bokoch, G. M., & Chernoff, J.
Venue
Current Biology
Publisher
Elsevier BV
Published
1997-03
Volume
7
Issue
3
Pages
202-210
ISSN
0960-9822
DOI
10.1016/s0960-9822(97)70091-5
Cited by
603
References
0
Language
en
Licence
Funders
  • American Chemical Society
  • National Institutes of Health
  • National Cancer Institute

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