THYMOCYTE ACTIVATION INDUCES THE ASSOCIATION OF THE PROTO-ONCOPROTEINC-CBL AND RAS GTPASE-ACTIVATING PROTEIN WITH CD5

Studies of knockout mice indicate that the glycoprotein CD5, which is expressed on T cells, most thymocytes and a subset of B cells, down-re gulates TCR-and B cell receptor (BCR)-mediated signaling. CD5 is assoc iated with the TCR and BCR, and is phosphorylated on cytoplasmic tyros ine 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-oncoprote in c-cbl associates with CD5 in pervanadate-stimulated thymocytes, and reprecipitation analysis demonstrates that the major proportion of CD 5-associated pp120 is c-cbl. The GTPase-activating protein for ras (ra s GAP), which is not tyrosine phosphorylated following CD5 cross-linki ng, associates with CD5 in pervanadate-stimulated thymocytes. Using ty rosine-phosphorylated peptides we show that ras GAP interacts in an SH 2-mediated manner with the phosphorylated Y429SQP sequence of CD5. Bot h c-cbl and ras GAP have been proposed to suppress receptor-mediated s ignaling, and may contribute to CD5-mediated suppression of TCR or BCR signaling.