Plas D R, Johnson R, Pingel J T, Matthews R J, Dalton M, Roy G, Chan A C, Thomas M L
Howard Hughes Medical Institute, Center for Immunology, Washington University Medical School, St Louis, Missouri 63110, USA.
Science. 1996 May 24;272(5265):1173-6. doi: 10.1126/science.272.5265.1173.
The threshold at which antigen triggers lymphocyte activation is set by the enzymes that regulate tyrosine phosphorylation. Upon T cell activation, the protein tyrosine phosphatase SHP-1 was found to bind to the protein tyrosine kinase ZAP-70. This interaction resulted in an increase in SHP-1 phosphatase activity and a decrease in ZAP-70 kinase activity. Expression of a dominant negative mutant of SHP-1 in T cells increased the sensitivity of the antigen receptor. Thus, SHP-1 functions as a negative regulator of the T cell antigen receptor and in setting the threshold of activation.
抗原触发淋巴细胞激活的阈值由调节酪氨酸磷酸化的酶设定。在T细胞激活后，发现蛋白酪氨酸磷酸酶SHP-1与蛋白酪氨酸激酶ZAP-70结合。这种相互作用导致SHP-1磷酸酶活性增加，ZAP-70激酶活性降低。在T细胞中表达SHP-1的显性负性突变体增加了抗原受体的敏感性。因此，SHP-1作为T细胞抗原受体的负调节因子，并在设定激活阈值中发挥作用。
