Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1

Ratna K Vadlamudi, Feng Li, Liana Adam, Diep Nguyen, Yasutaka Ohta, Thomas P. Stossel, Rakesh Kumar

Research output: Contribution to journalArticle

233 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)681-690
Number of pages10
JournalNature Cell Biology
Volume4
Issue number9
DOIs
StatePublished - Sep 2002
Externally publishedYes

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Filamins
p21-Activated Kinases
Actins
Binding Sites
Phosphorylation
Tandem Repeat Sequences
Protein-Serine-Threonine Kinases
GTP Phosphohydrolases
Serine

ASJC Scopus subject areas

  • Cell Biology

Cite this

Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1. / Vadlamudi, Ratna K; Li, Feng; Adam, Liana; Nguyen, Diep; Ohta, Yasutaka; Stossel, Thomas P.; Kumar, Rakesh.

In: Nature Cell Biology, Vol. 4, No. 9, 09.2002, p. 681-690.

Research output: Contribution to journalArticle

Vadlamudi, RK, Li, F, Adam, L, Nguyen, D, Ohta, Y, Stossel, TP & Kumar, R 2002, 'Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1', Nature Cell Biology, vol. 4, no. 9, pp. 681-690. https://doi.org/10.1038/ncb838
Vadlamudi, Ratna K ; Li, Feng ; Adam, Liana ; Nguyen, Diep ; Ohta, Yasutaka ; Stossel, Thomas P. ; Kumar, Rakesh. / Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1. In: Nature Cell Biology. 2002 ; Vol. 4, No. 9. pp. 681-690.
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