BIOCHEMICAL-ANALYSIS OF P120 130 - A PROTEIN-TYROSINE KINASE SUBSTRATE RESTRICTED TO T-CELLS AND MYELOID-CELLS/

T cell activation is mediated by a cascade of intracellular events inv olving protein-tyrosine kinases and their substrates. p56(lck) and p59 (fyn) are protein-tyrosine kinases that associate with CD4/CD8 and the TCR zeta/CD3 complex, respectively. We previously reported the appear ance of a protein doublet at 120 and 130 kDa that preferentially assoc iates with p59(fyn) and undergoes tyrosine phosphorylation upon recept or ligation. In this paper, we demonstrate that p120/130 is a novel pr otein that is restricted in expression to T cells, thymocytes and myel oid cells. Internal peptide sequencing and immunoblotting using an ant i-p120/130 antisera showed that p120/130 is a unique protein that is d istinct from p130(cas) and p125(cbl). By contrast, p120 and p130 share d similar peptide patterns and are structurally related. Alkaline phos phatase digestion of precipitates showed that they are not related due to phosphorylation. p120/130 was found to associate constitutively wi th a 55-kDa protein of unknown identity, but which is distinct from p5 6(lck) and Shc. p120/130 also undergoes a unique kinetics of phosphory lation and associates with the Ag receptor in response to TCR ligation . In keeping with the association with p59(fyn), T cells from p59(fyn) -negative mice exhibit reduced phosphorylation of the protein. p120/13 0 therefore represents a novel TCR associated intracellular molecule w ith potential to play a role in T cell signaling.