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| The EMBO Journal
(2000) 19, 4589–4600, doi:10.1093/emboj/19.17.4589 |
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| Scar/WAVE-1, a Wiskott–Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold |
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| Ryan S. Westphal1, 3, Scott H. Soderling1, 3, Neal M. Alto2, Lorene K. Langeberg1 and John D. Scott1 |
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1 Howard Hughes Medical Institute, Vollum Institute, The Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098, USA 2 Department of Cellular and Developmental Biology, The Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098, USA 3 R.S.Westphal and S.H.Soderling contributed equally to this work To whom correspondence should be addressed John D. Scott, scott@ohsu.edu Received 16 May 2000; Revised 9 June 2000; Accepted 5 July 2000. |
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| Abstract |
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| 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. |
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| Keywords: AKAP, anchoring protein, cytoskeleton, protein kinase targeting, signal transduction |
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