Catch a WAVE

Science's STKE  12 Sep 2000:
Vol. 2000, Issue 49, pp. tw2
DOI: 10.1126/stke.2000.49.tw2

During a search for proteins that could bind to both tyrosine kinases and serine/threonine kinases, Westphal et al. found WAVE-1, a member of the Wiskott-Aldrich syndrome protein (WASP) family of molecular scaffolds. WAVE-1 from brain extracts bound the SH3 domain of the Abelson tyrosine kinase (Abl) fused to glutathione S-transferase (GST) and also bound to protein kinase A (PKA). The PKA-binding domain of WAVE-1 overlapped with the actin-binding domain, and PKA competed for actin in binding to a WAVE-1/GST fusion protein. WAVE coimmunoprecipitated with PKA and Abl from brain extracts and recruited PKA and Abl to sites of actin rearrangement in cells treated with platelet-derived growth factor. Furthermore, WAVE-1 interacted with other WAVE isoforms, which may explain how WAVE-1 can recruit PKA to sites of actin reorganization despite exhibiting mutually exclusive in vitro binding. With these additional binding partners, the WASP family of molecular scaffolds brings not only the small guanosine trisphosphatases of the Rho family, but also second messenger-regulated protein kinases (PKA) and non-receptor tyrosine kinases to sites of actin reorganization.

Westphal, R.S., Soderling, S.H., Alto, N.M., Langeberg, L.K., and Scott, J.D. (2000) Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold. EMBO J. 19: 4589-4600. [Abstract] [Full Text]