Article abstract
Nature Cell Biology 4, 681 - 690 (2002)
Published online: 27 August 2002 | doi:10.1038/ncb838
Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1
Ratna K. Vadlamudi1, Feng Li1, Liana Adam1, Diep Nguyen1, Yasutaka Ohta2, Thomas P. Stossel2 & Rakesh Kumar1
Abstract
The serine/threonine kinase p21-activated kinase 1 (Pak1) controls the actin cytoskeletal and ruffle formation through mechanisms that are independent of GTPase activity. Here we identify filamin FLNa as a Pak1-interacting protein through a yeast two-hybrid screen using the amino terminus of Pak1 as a bait. FLNa is stimulated by physiological signalling molecules to undergo phosphorylation by Pak1 and to interact and colocalize with endogenous Pak1 in membrane ruffles. The ruffle-forming activity of Pak1 is functional in FLNa-expressing cells but not in FLNa-deficient cells. In FLNa, the Pak1-binding site involves tandem repeat 23 in the carboxyl terminus and phosphorylation takes place on serine 2152. The FLNa-binding site in Pak1 is localized between amino acids 52 and 132 in the conserved Cdc42/Rac-interacting (CRIB) domain; accordingly, FLNa binding to the CRIB domain stimulates Pak1 kinase activity. Our results indicate that FLNa may be essential for Pak1-induced cytoskeletal reorganization and that the two-way regulatory interaction between Pak1 and FLNa may contribute to the local stimulation of Pak1 activity and its targets in cytoskeletal structures.
- Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA
- Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Correspondence to: Rakesh Kumar1 e-mail: rkumar@mdanderson.org
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