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FEBS Lett. 2003 Aug 28;550(1-3):119-23.

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

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Department of Molecular Medicine, Baker Laboratory, Cornell University, Veterinary Medical Center, Ithaca, NY 14853, USA.


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.

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