The Src family of nonreceptor tyrosine kinases is negatively regulated by tyrosine phosphorylation by the Csk kinase. Src is associated with the intracellular leaflet of the plasma membrane through lipid modifications, but Csk lacks any intrinsic means for associating with the membrane. Kawabuchi et al. identified a transmembrane protein, Csk-binding protein (Cbp), that could be coprecipitated with Csk from brain lysates. Cbp is phosphorylated on tyrosine residues, ubiquitously expressed, and enriched in the detergent-insoluble membrane fraction. Tyrosine 314 was found to be essential for interaction with Csk and for proper recruitment of Csk to the plasma membrane in transfected cells. Overexpression of Cbp inhibited Src kinase activity in cells, and this inhibition was not present in Csk-deficient cells. Their data suggest a functional role for Cbp in regulating Src activity through the recruitment of Csk to the membrane where it phosphorylates and inhibits Src activity.
Kawabuchi, M., Satomi, Y., Takao, T., Shimonishi, Y., Nada, S., Nagai, K., Tarakhovsky, A., and Okada, M. (2000) Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases. Nature 404: 999-1003. [Online Journal]