Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ca2+/calmodulin-dependent protein kinase type Gr (CaM kinase-Gr) is a Ca2+/calmodulin-dependent protein kinase which is enriched in the brain and thymus. In this study, we examined the expression of CaM kinase-Gr in human lymphocytes and the regulation of its catalytic activity by antigen receptor signaling. CaM kinase-Gr was found selectively expressed in T lymphocytes in a developmentally regulated manner. It was present at severalfold higher levels in immature thymocytes (CD3low, CD4+CD8+) relative to mature thymocytes (CD3high, CD4+CD8-/CD8+CD4-) or to circulating T lymphocytes. The kinase was preferentially expressed in CD4+ T lymphocytes, but was not detected in B lymphocytes or in monocytes. The impact of T cell antigen receptor-CD3 complex (TCR.CD3) signaling on kinase activity was examined using Jurkat human leukemic T lymphocytes as a model. Treatment of Jurkat cells with anti TCR.CD3 monoclonal antibody induced rapid autophosphorylation of the kinase on serine residues and a dramatic, autophosphorylation-dependent enhancement of both Ca2+/calmodulin-dependent and autonomous kinase activity. Enzyme autophosphorylation and activation were dependent on the influx of extracellular Ca2+ following receptor signaling but could not be induced by an influx of extra-cellular Ca2+ triggered by ionophores, indicating that additional signals delivered via TCR.CD3 contribute to the activation of CaM kinase-Gr. These findings suggest a role for CaM kinase-Gr in T lymphocyte development and activation and indicate the presence of stringent regulatory mechanisms governing the activity of this kinase in situ.
 ...
PMID:Expression of a Ca2+/calmodulin-dependent protein kinase, CaM kinase-Gr, in human T lymphocytes. Regulation of kinase activity by T cell receptor signaling. 839 99

We investigated specific signaling events initiated after T cell triggering through the costimulatory surface receptors CD2 and CD28 as compared with activation via the Ag receptor (TCR/CD3). We therefore followed the phosphorylation of stathmin, a ubiquitous cytoplasmic phosphoprotein proposed as a general relay integrating diverse intracellular signaling pathways through the combinatorial phosphorylation of serines 16, 25, 38, and 63, the likely physiologic substrates for Ca2+/calmodulin (CaM)-dependent kinases, mitogen-activated protein (MAP) kinase, cyclin-dependent kinases (cdks), and protein kinase A, respectively. We addressed the specific protein kinase systems involved in the CD2 pathway of T cell activation through the analysis of stathmin phosphorylation patterns in exponentially growing Jurkat T cells, as revealed by phosphopeptide mapping. Stimulation via CD2 activated multiple signal transduction pathways, resulting in phosphorylation of distinct sites of stathmin, the combination of which only partially overlaps the CD3- and CD28-induced patterns. The partial redundancy of the three T cell activation pathways was evidenced by the phosphorylation of Ser25 and Ser38, substrates of MAP kinases and of the cdk family kinase(s), respectively. Conversely, the phosphorylation of Ser16 of stathmin was observed in response to both CD2 and CD28 triggering, but not CD3 triggering, with a kinetics compatible with the lasting activation of CaM kinase II in response to CD2 triggering. In vitro, Ser16 of recombinant human stathmin was phosphorylated also by purified CaM kinase II, and in vivo, CaM kinase II activity was indeed stimulated in CD2-triggered Jurkat cells. Altogether, our results favor an association of CaM kinase II activity with costimulatory signals of T lymphocyte activation and phosphorylation of stathmin on Ser16.
 ...
PMID:Serine 16 of stathmin as a cytosolic target for Ca2+/calmodulin-dependent kinase II after CD2 triggering of human T lymphocytes. 968 69

The outcome of thymocyte selection is influenced by the nature of Ca2+ signals transduced by the TCR. Robust Ca2+ responses characterize high-affinity, negatively selecting peptide/TCR interactions, while modest responses typify lower-affinity, positively selecting interactions. To elucidate mechanisms by which thymocytes decode distinct Ca2+ signals, we examined selection events in mice lacking Ca2+/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr), which is enriched in thymocytes. CaMKIV/Gr-deficient thymocytes exhibited impaired positive selection and defective Ca2+-dependent gene transcription. Significantly, CaMKIV/Gr deficiency raised the selection threshold of peptide/TCR interactions such that a peptide that normally induced weak negative selection instead promoted positive selection. These results demonstrate an important role for CaMKIV/Gr in sensitizing thymocytes to selection by low-affinity peptides.
 ...
PMID:Requirement for Ca2+/calmodulin-dependent kinase type IV/Gr in setting the thymocyte selection threshold. 1171 90