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

@article{Vadlamudi2002FilaminIE,
  title={Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1},
  author={Ratna K. Vadlamudi and Feng Li and Liana Adam and Diep N. Nguyen and Yasutaka Ohta and Thomas Peter Stossel and Rakesh Kumar},
  journal={Nature Cell Biology},
  year={2002},
  volume={4},
  pages={681-690}
}
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… 

Adapter protein SH2B1beta binds filamin A to regulate prolactin-dependent cytoskeletal reorganization and cell motility.

A model for PRL-dependent regulation of the actin cytoskeleton that integrates the findings with previous studies is proposed and found that in addition to two actin-binding domains, SH2B1β has a FLNa-binding domain that binds directly to repeats 17-23 of FLNa.

p21-Activated Kinase 1 Regulates Microtubule Dynamics by Phosphorylating Tubulin Cofactor B

A novel role for TCoB and Pak1 is revealed in regulating microtubule dynamics through an elusive mechanism that was overexpressed and phosphorylated in breast tumors and revealed a phenotype reminiscent of cells overexpressing Pak1.

Constitutive p21-activated kinase (PAK) activation in breast cancer cells as a result of mislocalization of PAK to focal adhesions.

It is shown that endogenous PAK is constitutively activated in certain breast cancer cell lines and that this activePAK is mislocalized to atypical focal adhesions in the absence of high levels of activated Rho GTPases.

Nuclear Localization and Chromatin Targets of p21-activated Kinase 1*

Investigations provide proof-of-principle evidence that Pak1 could influence the expression of its putative chromatin targets in both a positive and a negative manner, opening new avenues to further the search for nuclear Pak1 functions and identify putative Pak1-interacting nuclear proteins.

Essential role of CIB1 in regulating PAK1 activation and cell migration

It is demonstrated that endogenous CIB1 is required for regulated adhesion-induced PAK1 activation and preferentially induces aPAK1-dependent pathway that can negatively regulate cell migration.

Trihydrophobin 1 Interacts with PAK1 and Regulates ERK/MAPK Activation and Cell Migration*

A model is proposed in which trihydrophobin 1 interacts with PAK1 and specifically restricts the activation of MAPK modules through the upstream region of the MAPK pathway, thereby influencing cell migration.

Ribosomal S6 Kinase (RSK) Regulates Phosphorylation of Filamin A on an Important Regulatory Site

The characterization of the cytoskeletal protein filamin A (FLNa) as a membrane-associated RSK target and substantial evidence that RSK phosphorylates FLNa on Ser2152 in vivo are provided, suggesting a novel role for RSK in the regulation of the actin cytoskeleton.

Biology of the p21-activated kinases.

  • G. Bokoch
  • Biology
    Annual review of biochemistry
  • 2003
A key role is proposed for PAK action in coordinating the dynamics of the actin and microtubule cytoskeletons during directional motility of cells, as well as in other functions requiring cytOSkeletal polarization.

The endocytic adapter E-Syt2 recruits the p21 GTPase activated kinase PAK1 to mediate actin dynamics and FGF signalling

The data suggest that PAK1 interacts with phospholipid membrane domains via E-Syt2, where it may cooperate in the E- Syt2-dependent endocytosis of activated FGFR1 by modulating cortical actin stability.
...

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