Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold

EMBO J. 2000 Sep 1;19(17):4589-600. doi: 10.1093/emboj/19.17.4589.

Abstract

WAVE proteins are members of the Wiskott-Aldrich syndrome protein (WASP) family of scaffolding proteins that coordinate actin reorganization by coupling Rho-related small molecular weight GTPases to the mobilization of the Arp2/3 complex. We identified WAVE-1 in a screen for rat brain A kinase-anchoring proteins (AKAPs), which bind to the SH3 domain of the Abelson tyrosine kinase (Abl). Recombinant WAVE-1 interacts with cAMP-dependent protein kinase (PKA) and Abl kinases when expressed in HEK-293 cells, and both enzymes co-purify with endogenous WAVE from brain extracts. Mapping studies have defined binding sites for each kinase. Competition experiments suggest that the PKA-WAVE-1 interaction may be regulated by actin as the kinase binds to a site overlapping a verprolin homology region, which has been shown to interact with actin. Immunocytochemical analyses in Swiss 3T3 fibroblasts suggest that the WAVE-1 kinase scaffold is assembled dynamically as WAVE, PKA and Abl translocate to sites of actin reorganization in response to platelet-derived growth factor treatment. Thus, we propose a previously unrecognized function for WAVE-1 as an actin-associated scaffolding protein that recruits PKA and Abl.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • DNA Primers
  • Immunohistochemistry
  • Mice
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / metabolism*
  • Molecular Sequence Data
  • Oncogene Proteins v-abl / metabolism
  • Precipitin Tests
  • Protein Binding
  • Protein Isoforms / metabolism
  • Rats
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Wiskott-Aldrich Syndrome / metabolism*
  • Wiskott-Aldrich Syndrome Protein Family

Substances

  • DNA Primers
  • Microfilament Proteins
  • Oncogene Proteins v-abl
  • Protein Isoforms
  • Recombinant Proteins
  • Wasf1 protein, mouse
  • Wiskott-Aldrich Syndrome Protein Family
  • Cyclic AMP-Dependent Protein Kinases