Selective CD28pYMNM mutations implicate phosphatidylinositol 3-kinase in CD86-CD28-mediated costimulation

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• 作者：Yun-Cai Cai ; Daniel Cefai ; Helga Schneider ; Monika Raab ; Nasrin Nabavi ; Christopher E. Rudd
• 刊名：Immunity
• 出版年：1995
• 出版时间：October 1995
• 年：1995
• 卷：3
• 期：4
• 页码：417-426
• 全文大小：1442 K

文摘

CD28 costimulatory signals are required for lymphokine production and T cell proliferation. CD28 signaling recruits the intracellular proteins PI 3-kinase, ITK, and GRB-2/SOS. PI 3-kinase and GRB-2/SOS bind the CD28 cytoplasmic pYMNM motif via SH2 domains. We generated CD28 pYMNM mutants and found that Y191 mutation (Y¹⁹¹CD28F) disrupted both PI 3-kinase and GRB-2 binding, while M¹⁹⁴ mutation (M¹⁹⁴CD28C) disrupted only PI 3-kinase binding. Both mutants still bound ITK. We have assessed the ability of these selective mutants to support IL-2 production upon TCRξ/ CD3 ligation in the presence of CHO-CD86 (B7-2) cells. Both Y¹⁹¹CD28F and M¹⁹⁴CD28C mutants failed to generate IL-2. These data directly implicate PI 3-kinase in CD28-mediated costimulation leading to IL-2 secretion. Wortmannin, an inhibitor of PI 3-kinase, induced cell apoptosis and as such was unsuitable for use in this study.