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 T cells, 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.