51. The Cbl proteins are binding partners for the Cool/Pix family of p21-activated kinase-binding proteins.
- Author
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Flanders JA, Feng Q, Bagrodia S, Laux MT, Singavarapu A, and Cerione RA
- Subjects
- Amino Acid Sequence, Animals, Binding, Competitive, Breast Neoplasms metabolism, COS Cells, Carrier Proteins genetics, Cell Cycle Proteins genetics, Female, Guanine Nucleotide Exchange Factors genetics, Humans, Molecular Sequence Data, Phosphoproteins genetics, Protein Binding, Protein Serine-Threonine Kinases genetics, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-cbl, Rho Guanine Nucleotide Exchange Factors, Tumor Cells, Cultured, Two-Hybrid System Techniques, p21-Activated Kinases, src Homology Domains physiology, Adaptor Proteins, Signal Transducing, Carrier Proteins metabolism, Cell Cycle Proteins metabolism, Guanine Nucleotide Exchange Factors metabolism, Phosphoproteins metabolism, Protein Serine-Threonine Kinases metabolism, Ubiquitin-Protein Ligases
- Abstract
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.
- Published
- 2003
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