Activation of the multicomponent antigen receptor in T cells (TCR) results in rapid activation of protein tyrosine and serine kinase pathways. The tyrosine kinase pathway has previously been shown to be activated before phospholipase C. We have used the tyrosine kinase inhibitor, herbimycin, to demonstrate that inhibition of tyrosine phosphorylation results in inhibition of TCR-mediated phosphoinositide hydrolysis. These results suggest that the tyrosine phosphorylation pathway regulates phospholipase C activity. Using digitonin as a detergent to solubilize a murine T cell hybridoma, we have demonstrated that the protein tyrosine kinase fyn is noncovalently associated with the TCR. This kinase may be responsible for the intracellular tyrosine phosphorylations detected after TCR engagement. In immature thymocytes, we detect a constitutive tyrosine phosphorylation of the TCR zeta chain. When the cells are removed from the thymus and cultured in suspension, the zeta chain dephosphorylates and TCR levels increase. These events correlate with an increased capability to respond to TCR ligation with increases in intracellular calcium. Ligation of surface immunoglobulin, the B cell antigen receptor, also results in an increase in tyrosine phosphorylation of intracellular substrates in B cells.
