DIFFERENTIAL REGULATION OF P72(SYK) EXPRESSION IN NAIVE AND PROLIFERATING CD4(-)CD8(-CELLS() T)

A well-known consequence of TCR stimulation in proliferating T cells i s cell death by apoptosis. We have previously shown that the extent of tyrosine phosphorylation of TCR zeta, CD3 gamma, and CD3 epsilon subu nits in proliferating CD4(-)CD8(+) T cells after TCR stimulation was d ecreased when compared to similarly stimulated naive T cells expressin g the same TCR. Furthermore, these differences correlated with a decre ase in the specific kinase activity of p56(lck) and p59(fyn), with a c orresponding increase in the specific kinase activity of p50(csk), a n egative regulator of src-family tyrosine kinases. In this study we det ermined whether kinases that bind tyrosine phosphorylated TCR zeta cha in were differentially regulated in naive and proliferating cells. Che mically synthesized cytoplasmic domains of the TCR zeta chain were ful ly phosphorylated ill vitro with p56(lck) and used to precipitate TCR zeta binding proteins in naive and proliferating cells. Using this met hod we found that both ZAP-70 and p72(syk) bound tyrosine phosphorylat ed TCR zeta very efficiently. More interestingly, p72(syk) was found t o be expressed only in naive but not proliferating cells. Kinetic stud ies indicate that more than 48 hr of activation was required for ceasa tion of p72(syk) expression. We also showed that the inability to dete ct p72(syk) expression in proliferating cells was not due to its trans location to cytoskeletal compartments in proliferating cells. We propo se that the differential regulation of ZAP-70 and p72(syk) in naive an d proliferating cells may contribute to the uncoupling of the TCR sign aling pathway from downstream signaling events leading to distinct fun ctional outcomes in these two cell types after TCR stimulation. Copyri ght (C) 1996 Elsevier Science Ltd