Sun, 20 Jul 2008 21:41:58 BST CiteULike: neils antigen http://www.citeulike.org/user/neils/tag/antigen CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/neils/article/2054447 <i>J Immunol, Vol. 175, No. 2. (Jul 2005), pp. 656-664.</i><br /><br />T cell development is regulated at two critical checkpoints that involve signaling events through the TCR. These signals are propagated by kinases of the Src and Syk families, which activate several adaptor molecules to trigger Ca(2+) release and, in turn, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activation. In this study, we show that a constitutively active form of CaMKII antagonizes TCR signaling and impairs positive selection of thymocytes in mice. Following TCR engagement, active CaMKII decreases TCR-mediated CD3zeta chain phosphorylation and ZAP70 recruitment, preventing further downstream events. Therefore, we propose that CaMKII belongs to a negative-feedback loop that modulates the strength of the TCR signal through the tyrosine phosphatase Src homology 2 domain-containing phosphatase 2 (SHP-2). Active Ca2+/calmodulin-dependent protein kinase II gamma B impairs positive selection of T cells by modulating TCR signaling. Maureen Mcgargill Leslie Sharp Jack Bui Stephen Hedrick Sébastien Calbo J Immunol, Vol. 175, No. 2. (Jul 2005), pp. 656-664. 2007-12-04T03:22:10-00:00 2005 J Immunol 175 2 656 664 animal antigen article-predikin c57bl ca2-calmodulin calcium cd3 cell dependent differentiation domain female fluid homology human inbred intracellular isoenzymes kinase knockout line lymphocyte male mice p56lck peptide phosphorylation protein protein-tyrosine-phosphatase receptor signal signaling specific src subset t-cell t-lymphocyte transduction transgenic tumor tyrosine