Musci M A, Hendricks-Taylor L R, Motto D G, Paskind M, Kamens J, Turck C W, Koretzky G A
Graduate Program in Immunology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
J Biol Chem. 1997 May 2;272(18):11674-7. doi: 10.1074/jbc.272.18.11674.
Previous work has demonstrated that SLP-76, a Grb2-associated tyrosine-phosphorylated protein, augments Interleukin-2 promoter activity when overexpressed in the Jurkat T cell line. This activity requires regions of SLP-76 that mediate protein-protein interactions with other molecules in T cells, suggesting that SLP-76-associated proteins also function to regulate signal transduction. Here we describe the molecular cloning of SLAP-130, a SLP-76-associated phosphoprotein of 130 kDa. We demonstrate that SLAP-130 is hematopoietic cell-specific and associates with the SH2 domain of SLP-76. Additionally, we show that SLAP-130 is a substrate of the T cell antigen receptor-induced protein tyrosine kinases. Interestingly, we find that in contrast to SLP-76, overexpression of SLAP-130 diminishes T cell antigen receptor-induced activation of the interleukin-2 promoter in Jurkat T cells and interferes with the augmentation of interleukin-2 promoter activity seen when SLP-76 is overexpressed in these cells. These data suggest that SLP-76 recruits a negative regulator, SLAP-130, as well as positive regulators of signal transduction in T cells.
先前的研究表明，SLP-76是一种与Grb2相关的酪氨酸磷酸化蛋白，当在Jurkat T细胞系中过表达时，可增强白细胞介素-2启动子的活性。这种活性需要SLP-76中与T细胞中其他分子介导蛋白质-蛋白质相互作用的区域，这表明与SLP-76相关的蛋白质也参与调节信号转导。在此，我们描述了SLAP-130的分子克隆，它是一种与SLP-76相关的130 kDa磷蛋白。我们证明SLAP-130是造血细胞特异性的，并且与SLP-76的SH2结构域相关联。此外，我们表明SLAP-130是T细胞抗原受体诱导的蛋白酪氨酸激酶的底物。有趣的是，我们发现与SLP-76相反，SLAP-130的过表达会降低Jurkat T细胞中T细胞抗原受体诱导的白细胞介素-2启动子的激活，并干扰在这些细胞中过表达SLP-76时观察到的白细胞介素-2启动子活性的增强。这些数据表明，SLP-76在T细胞中募集了一个负调节因子SLAP-130以及信号转导的正调节因子。
