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

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.
Mesh Terms:
3T3 Cells, Amino Acid Sequence, Animals, Base Sequence, Cyclic AMP-Dependent Protein Kinases, DNA Primers, Immunohistochemistry, Mice, Microfilament Proteins, Molecular Sequence Data, Oncogene Proteins v-abl, Precipitin Tests, Protein Binding, Protein Isoforms, Rats, Recombinant Proteins, Sequence Homology, Amino Acid, Signal Transduction, Wiskott-Aldrich Syndrome, Wiskott-Aldrich Syndrome Protein Family
EMBO J.
Date: Sep. 01, 2000
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