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The Cbl proteins are binding partners for the Cool/Pix family of p21‐activated kinase‐binding proteins
Author(s) -
Flanders James A,
Feng Qiyu,
Bagrodia Shubha,
Laux Maria T,
Singavarapu Avinash,
Cerione Richard A
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00853-6
Subject(s) - pleckstrin homology domain , regulator , microbiology and biotechnology , plasma protein binding , yeast , signal transduction , kinase , chemistry , biology , biochemistry , gene
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.