Research Article 1663 Characterisation of IRTKS, a novel IRSp53/MIM family actin regulator with distinct filament bundling properties Thomas H. Millard*, John Dawson and Laura M. Machesky‡ School of Biosciences, University of Birmingham, Birmingham, B15 2TT, UK *Present address: University of Bristol, Dept. of Biochemistry, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK ‡Author for correspondence (e-mail:
[email protected]) Accepted 12 March 2007 Journal of Cell Science 120, 1663-1672 Published by The Company of Biologists 2007 doi:10.1242/jcs.001776 Summary IRSp53 is a scaffold protein that contains an IRSp53/MIM resembles a WASP-homology 2 (WH2) motif. Addition of homology domain (IMD) that bundles actin filaments and the Ct extension to IRSp53 causes an apparent shortening interacts with the small GTPase Rac. IRSp53 also binds to of bundles induced by the IMD in vitro, and in cultured the small GTPase Cdc42 and to Scar/WAVE and cells, suggesting that the Ct extension of IRTKS modulates Mena/VASP proteins to regulate the actin cytoskeleton. We the organising activity of the IMD. Lastly, we could not have characterised a novel IMD-containing protein, insulin detect actin monomer sequestration by the Ct extension of receptor tyrosine kinase substrate (IRTKS), which has IRTKS as would be expected with a conventional WH2 widespread tissue distribution, is a substrate for the insulin motif, but it did interact with actin filaments. receptor and binds Rac. Unlike IRSp53, IRTKS does not interact with Cdc42. Expression of IRTKS induces clusters Supplementary material available online at of short actin bundles rather than filopodia-like http://jcs.biologists.org/cgi/content/full/120/9/1663/DC1 protrusions.