Chan A C, Dalton M, Johnson R, Kong G H, Wang T, Thoma R, Kurosaki T
Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110, USA.
EMBO J. 1995 Jun 1;14(11):2499-508. doi: 10.1002/j.1460-2075.1995.tb07247.x.
ZAP-70 is a protein tyrosine kinase (PTK) required for T-cell development and T-cell antigen receptor (TCR) function. ZAP-70 is associated with the phosphorylated antigen receptor and undergoes tyrosine phosphorylation following receptor activation. We demonstrate here that tyrosine phosphorylation of ZAP-70 results in an increase in its catalytic activity and that this activation is mediated by the phosphorylation of tyrosine residue 493 by the src family of PTKs. The activity of baculoviral expressed ZAP-70 was up-regulated 10-fold when ZAP-70 was co-infected and phosphorylated by the src family PTK, lck. Mutation of Y493 alone abrogated the ability of ZAP-70 to be activated by lck. Moreover, we demonstrate that phosphorylation of Y493 and activation of ZAP-70 is required for antigen receptor-mediated induction of interleukin-2 (IL-2) secretion in lymphocytes.
ZAP-70是一种蛋白酪氨酸激酶（PTK），是T细胞发育和T细胞抗原受体（TCR）功能所必需的。ZAP-70与磷酸化的抗原受体相关，并在受体激活后发生酪氨酸磷酸化。我们在此证明，ZAP-70的酪氨酸磷酸化导致其催化活性增加，并且这种激活是由src家族的PTK将酪氨酸残基493磷酸化介导的。当ZAP-70与src家族的PTK lck共同感染并被其磷酸化时，杆状病毒表达的ZAP-70的活性上调了10倍。单独将Y493突变会消除ZAP-70被lck激活的能力。此外，我们证明Y493的磷酸化和ZAP-70的激活是淋巴细胞中抗原受体介导的白细胞介素-2（IL-2）分泌诱导所必需的。
