Fang N, Motto D G, Ross S E, Koretzky G A
Graduate Program in Immunology, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
J Immunol. 1996 Nov 1;157(9):3769-73.
SLP-76 (SH2 domain leukocyte protein of 76 kDa) is a recently identified substrate of the TCR-stimulated protein tyrosine kinases that functions in the signal transduction cascade linking the TCR with IL-2 gene expression. In this report, we demonstrate that engagement of the TCR results in tyrosine phosphorylation of SLP-76 in its amino-terminal acidic region. Two tyrosines (Y113 and Y128) fall within an identical five amino-acid motif and are shown to be phosphorylated upon TCR ligation. Although mutation of either Y113 and Y128 has a minimal effect on SLP-76 function, mutation of both residues decreases significantly the ability of SLP-76 to promote T cell activation. A third tyrosine within the amino-terminal region (Y145) appears to be the most important for optimal SLP-76 function, as altering it alone to phenylalanine has a potent impact on SLP-76 augmentation of NFAT promoter activity.
SLP - 76（76 kDa的含SH2结构域白细胞蛋白）是最近发现的TCR刺激的蛋白酪氨酸激酶的底物，在将TCR与IL - 2基因表达联系起来的信号转导级联反应中发挥作用。在本报告中，我们证明TCR的激活导致SLP - 76在其氨基末端酸性区域发生酪氨酸磷酸化。两个酪氨酸（Y113和Y128）位于相同的五个氨基酸基序内，并且在TCR连接后显示被磷酸化。虽然Y113和Y128中的任何一个发生突变对SLP - 76功能的影响最小，但两个残基都发生突变会显著降低SLP - 76促进T细胞活化的能力。氨基末端区域内的第三个酪氨酸（Y145）似乎对最佳SLP - 76功能最为重要，因为仅将其改变为苯丙氨酸就会对SLP - 76增强NFAT启动子活性产生强烈影响。
