Thymocyte activation induces the association of the proto-oncoprotein c-cbl and ras GTPase-activating protein with CD5.

Studies of knockout mice indicate that the glycoprotein CD5, which is expressed on Tcells, most thymocytes and a subset of B cells, down-regulates TCR- and B cell receptor (BCR)-mediated signaling. CD5 is associated with the TCR and BCR, and is phosphorylated on cytoplasmic tyrosine residues following antigen receptor ligation. Cross-linking of CD5 or pervanadate stimulation of thymocytes induces the association of a 120-kDa tyrosine-phosphorylated protein with CD5. The proto-oncoprotein c-cbl associates with CD5 in pervanadate-stimulated thymocytes, and reprecipitation analysis demonstrates that the major proportion of CD5-associated pp120 is c-cbl. The GTPase-activating protein for ras (ras GAP), which is not tyrosine phosphorylated following CD5 cross-linking, associates with CD5 in pervanadate-stimulated thymocytes. Using tyrosine-phosphorylated peptides we show that ras GAP interacts in an SH2-mediated manner with the phosphorylated Y429SQP sequence of CD5. Both c-cbl and ras GAP have been proposed to suppress receptor-mediated signaling, and may contribute to CD5-mediated suppression of TCR or BCR signaling.