Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases

The Src family of protein tyrosine kinases (Src-PTKs) is important in the r egulation of growth and differentiation of eukaryotic cells. The activity o f Src-PTKs in cells of different types is negatively controlled by Csk, whi ch specifically phosphorylates a conserved regulatory tyrosine residue at t he carboxy-terminal tail of the Src-PTKs(1-3). Csk is mainly cytoplasmic an d Src-PTKs are predominantly membrane-associated. This raises a question ab out the mechanism of interaction between these enzymes. Here we present Cbp -a transmembrane phosphoprotein that is ubiquitously expressed and binds sp ecifically to the SH2 domain of Csk. Cbp is involved in the membrane locali zation of Csk and in the Csk-mediated inhibition of c-Src. In the plasma me mbrane Cbp is exclusively localized in the GM1 ganglioside-enriched deterge nt-insoluble membrane domain, which is important in receptor-mediated signa lling(4-8). These findings reveal Cbp as a new component of the regulatory mechanism controlling the activity of membrane-associated Src-PTKs.