Raab M, Rudd C E
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Biochem Biophys Res Commun. 1996 May 6;222(1):50-7. doi: 10.1006/bbrc.1996.0696.
Ligation of the T cell receptor complex and CD4 leads to activation of the protein tyrosine kinases p56lck and p59fyn resulting in phosphorylation of TcR zeta chain and the recruitment of ZAP-70. In this study, we have reconstituted p56lck phosphorylation of TcR zeta and ZAP-70 recruitment in heterologous cells and examined the role of the tyrosine phosphatase HCP in regulating the process. Both p56lck and p59fyn induce significant phosphorylation of TcR zeta. However, under conditions of comparable p56lck and p59fyn expression, p56lck was found to induce three to four fold greater in vivo phosphorylation of TcR zeta. HCP dephosphorylated p56lck, ZAP-70 and the TcR zeta chain. Further, dephosphorylation of the different TcR zeta isoforms results in disruption of the interaction between TcR zeta and ZAP-70. These results indicate that HCP acts to negatively regulate signal transduction pathways in T cells.
T细胞受体复合物和CD4的连接导致蛋白酪氨酸激酶p56lck和p59fyn的激活，从而导致TcR ζ链的磷酸化以及ZAP-70的募集。在本研究中，我们在异源细胞中重建了TcR ζ的p56lck磷酸化和ZAP-70募集，并研究了酪氨酸磷酸酶HCP在调节该过程中的作用。p56lck和p59fyn均诱导TcR ζ的显著磷酸化。然而，在p56lck和p59fyn表达相当的条件下，发现p56lck在体内诱导的TcR ζ磷酸化程度要高三到四倍。HCP使p56lck、ZAP-70和TcR ζ链去磷酸化。此外，不同TcR ζ异构体的去磷酸化导致TcR ζ与ZAP-70之间的相互作用中断。这些结果表明，HCP起到负向调节T细胞信号转导途径的作用。
