The Cbl proteins are binding partners for the Cool/Pix family of p21-activated kinase-binding proteins

• Published in: FEBS Letters Vol. 550; no. 1; pp. 119 - 123
• Main Authors: Flanders, James A, Feng, Qiyu, Bagrodia, Shubha, Laux, Maria T, Singavarapu, Avinash, Cerione, Richard A
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 28.08.2003; Wiley
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Binding, Competitive; Breast cancer cell; Breast Neoplasms; Breast Neoplasms - metabolism; Carrier Proteins; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cbl; Cbl, Casitas B-lymphoma; Cdc42; Cell Cycle Proteins; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cool, cloned out of library; COS Cells; Female; Guanine Nucleotide Exchange Factors; Guanine Nucleotide Exchange Factors - genetics; Guanine Nucleotide Exchange Factors - metabolism; Humans; Molecular Sequence Data; p21-activated kinase; p21-Activated Kinases; PAK, p21-activated kinase; Phosphoproteins; Phosphoproteins - genetics; Phosphoproteins - metabolism; Pix, PAK-interactive exchange factor; Protein Binding; Protein Serine-Threonine Kinases; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-cbl; Rho Guanine Nucleotide Exchange Factors; SH3 domain; src Homology Domains; src Homology Domains - physiology; Tumor Cells, Cultured; Two-Hybrid System Techniques; Ubiquitin-Protein Ligases; SH3 domain; PAK, p21-activated kinase; p21-activated kinase; Cbl, Casitas B-lymphoma; Breast cancer cell; Cbl; Pix, PAK-interactive exchange factor; Cool, cloned out of library; Cdc42
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(03)00853-6

Members of the Cool protein family contain SH3, Dbl, and pleckstrin homology domains and are binding partners for the p21-activated kinase (PAK). Using the yeast two-hybrid screen, we identified Cbl-b as a Cool family binding partner. We co-immunoprecipitated endogenous Cool and Cbl-b from a variety of breast cancer cell lines. The Cool–Cbl-b interaction requires the SH3 domain of Cool and competes with the binding of PAK to Cool proteins. Expression of Cbl-b effectively blocks the ability of Cool-2 to stimulate PAK, thus providing an additional mechanism, aside from catalyzing receptor ubiquitination, by which Cbl-b acts as a negative regulator for signaling activities requiring PAK activation.