CMS: An adapter molecule involved in cytoskeletal rearrangements

CMS: An adapter molecule involved in cytoskeletal rearrangements

Laboratory of Molecular Oncology, The Rockefeller University, 1230 York Avenue, New York, NY 10021

Contributed by Hidesaburo Hanafusa

Abstract

Cas ligand with multiple Src homology (SH) 3 domains (CMS) is an ubiquitously expressed signal transduction molecule that interacts with the focal adhesion protein p130^Cas. CMS contains three SH3 in its NH₂ terminus and proline-rich sequences in its center region. The latter sequences mediate the binding to the SH3 domains of p130^Cas, Src-family kinases, p85 subunit of phosphatidylinositol 3-kinase, and Grb2. The COOH-terminal region contains putative actin binding sites and a coiled-coil domain that mediates homodimerization of CMS. CMS is a cytoplasmic protein that colocalizes with F-actin and p130^Cas to membrane ruffles and leading edges of cells. Ectopic expression of CMS in COS-7 cells resulted in alteration in arrangement of the actin cytoskeleton. We observed a diffuse distribution of actin in small dots and less actin fiber formation. Altogether, these features suggest that CMS functions as a scaffolding molecule with a specialized role in regulation of the actin cytoskeleton.

Footnotes

↵ * To whom reprint requests should be addressed. e-mail: kirschk{at}rockvax.rockefeller.edu.
↵ † Present address: Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF146277).
ABBREVIATIONS:

CMS,

Cas ligand with multiple Src homology 3 domains;

SH,

Src homology;

GST,

glutathione S-transferase;

TH,

two-hybrid;

CC,

coiled-coil;

WB,

Western blot;

FAK,

focal adhesion kinase