IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling

@article{Miki2000IRSp53IA,
  title={IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling},
  author={Hiroaki Miki and Hideki Yamaguchi and Shiro Suetsugu and Tadaomi Takenawa},
  journal={Nature},
  year={2000},
  volume={408},
  pages={732-735}
}
Neural Wiskott-Aldrich syndrome protein (N-WASP) functions in several intracellular events including filopodium formation, vesicle transport and movement of Shigella frexneri and vaccinia virus, by stimulating rapid actin polymerization through the Arp2/3 complex. N-WASP is regulated by the direct binding of Cdc42 (refs 7, 8 ), which exposes the domain in N-WASP that activates the Arp2/3 complex. A WASP-related protein, WAVE/Scar, functions in Rac-induced membrane ruffling; however, Rac does… 
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TLDR
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TLDR
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TLDR
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Mechanism of IRSp53 inhibition by 14-3-3
TLDR
A mechanism of phosphorylation-dependent inhibition of IR Sp53 by 14-3-3 is elucidated, which impedes the interactions of IRSp53 with membranes and downstream cytoskeletal effectors.
Mechanism of IRSp53 inhibition and combinatorial activation by Cdc42 and downstream effectors
TLDR
Using a fluorescence reporter assay, it is shown that human IRSp53 adopts a closed inactive conformation that opens synergistically with the binding of human Cdc42 to the CRIB–PR and effector proteins, such as the tumor-promoting factor Eps8, to the SH3 domain.
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References

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WAVE, a novel WASP‐family protein involved in actin reorganization induced by Rac
TLDR
It is concluded that WAVE plays a critical role downstream of Rac in regulating the actin cytoskeleton required for membrane ruffling.
N‐WASP, a novel actin‐depolymerizing protein, regulates the cortical cytoskeletal rearrangement in a PIP2‐dependent manner downstream of tyrosine kinases.
TLDR
It is concluded that N‐WASP transmits signals from tyrosine kinases to cause a polarized rearrangement of cortical actin filaments dependent on PIP2.
Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP
TLDR
It is demonstrated that before it can induce filopodium formation, Cdc42 must bind a WASP-related protein, N-WASP, that is richest in neural tissues but is expressed ubiquitously.
Identification of two human WAVE/SCAR homologues as general actin regulatory molecules which associate with the Arp2/3 complex.
TLDR
The identification of WAVE homologues suggests that WAVE family proteins have general function for regulating the actin cytoskeleton in many tissues.
Phosphorylation of WAVE Downstream of Mitogen-activated Protein Kinase Signaling*
TLDR
In various cancer cell lines, the amount of WAVE mobility shift was found to increase significantly, suggesting the importance ofWAVE hyperphosphorylation in the formation of membrane ruffles and oncogenic transformation.
Neural Wiskott–Aldrich syndrome protein is implicated in the actin‐based motility of Shigella flexneri
TLDR
It is shown that neural Wiskott–Aldrich syndrome protein (N‐WASP), which is a critical target for filopodium formation downstream of Cdc42, is required for assembly of the actin tail generated by intracellular S.flexneri.
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