CMS: An Adapter Molecule Involved in Cytoskeletal Rearrangements

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 11; pp. 6211 - 6216
• Main Authors: Kirsch, Kathrin H., Georgescu, Maria-Magdalena, Ishimaru, Satoshi, Hanafusa, Hidesaburo
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 25.05.1999; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Actins; Adaptor Proteins, Signal Transducing; Adult; Amino Acid Sequence; Animals; Antibodies; Binding sites; Biological Sciences; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line; Cell Membrane - physiology; Cell Membrane - ultrastructure; Cells; Cellular biology; Complementary DNA; COS Cells; Crk-Associated Substrate Protein; Cytoskeletal Proteins; Cytoskeleton - physiology; Cytoskeleton - ultrastructure; DNA; Female; Fetus; Gene Library; Humans; Molecular Sequence Data; Molecules; Organ Specificity; Phosphatidylinositol 3-Kinases - metabolism; Phosphoproteins - metabolism; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Proteins; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Retinoblastoma Protein - metabolism; Retinoblastoma-Like Protein p130; Ruffles; Sequence Alignment; Sequence Homology, Amino Acid; Signal Transduction; Transcription, Genetic; Transfection; Tumors; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.11.6211

Cas ligand with multiple Src homology (SH) 3 domains (CMS) is an ubiquitously expressed signal transduction molecule that interacts with the focal adhesion protein p130Cas. 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 p130Cas, 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 p130Cas 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.