Activation of Murine T-cells via Phospholipase-C l-Associated Protein Tyrosine Phosphorylation Is Reduced With Aging

Publisher Website
Google Scholar
Abstract
Cross-linking of the T-cell receptor (CD3) induces activation of tyrosine kinases and the subsequent phosphorylation of intracellular protein substrates. We examined whether early events in signal transduction through CD3 or CD3 × CD4 receptor ligation were altered in aged murine T-lymphocytes. Both calcium mobilization and tyrosine phosphorylation of phospholipase Cγl (PLCγl) were decreased in T-lymphocytes from old mice. In addition, there was less tyrosine phosphorylation of a 35/36 kDa protein both in whole cell lysates and in PLCγl immunoprecipitates from old mice. This 35/36 kDa phosphoprotein binds specifically to the SH2 domains of PLCγl. Using a fusion protein containing the SH2 domains of PLCγl and human IgGl heavy chain, we identified three additional proteinsthat bind to the SH2 domains which were tyrosine phosphorylated following CD3 × CD4 ligation to a lesser degree with age. The tyrosine phosphorylation of two phosphoproteins binding to a fusion protein consisting of the SH2 domains of GAP (ras GTPase-activating protein) and human IgGl heavy chain was also reduced with aging. The observed binding to SH2 domains was thiol redox sensitive. Thus, decreases in antioxidants with age may be responsible for inhibitory effects on PLCγl-phosphatidylinositol signaling through redox regulation of tyrosine phosphoproteins.

This publication has 0 references indexed in Scilit: