MOLECULAR-CLONING OF THE CDNA-ENCODING PP36, A TYROSINE-PHOSPHORYLATED ADAPTER PROTEIN SELECTIVELY EXPRESSED BY T-CELLS AND NATURAL-KILLER-CELLS

Activation of T and natural killer (NK) cells leads to the tyrosine ph osphorylation of pp36 and to its association with several signaling mo lecules, including phospholipase C gamma-1 and Grb2. Microsequencing o f peptides derived from purified rat pp36 protein led to the cloning, in rat and man, of cDNA encoding a T- and NK cell-specific protein wit h several putative Src homology 2 domain-binding motifs. A rabbit anti serum directed against a peptide sequence from the cloned rat molecule recognized tyrosine phosphorylated pp36 from pervanadate-treated rat thymocytes. When expressed in 293T human fibroblast cells and tyrosine -phosphorylated, pp36 associated with phospholipase C gamma-1 and Grb2 . Studies with GST-Grb2 fusion proteins demonstrated that the associat ion was specific for the Src homology 2 domain of Grb-2. Molecular clo ning of the gene encoding pp36 should facilitate studies examining the role of this adaptor protein in proximal signaling events during T an d NK cell activation.