Expression of a Ca2+/calmodulin-dependent protein kinase, CaM kinase-Gr, in human T lymphocytes. Regulation of kinase activity by T cell receptor signaling.
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.
Division of Immunology, Children's Hospital, Boston, Massachusetts.
S H
SH
Hanissian
M
M
Frangakis
M M
MM
Bland
S
S
Jawahar
T A
TA
Chatila
D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D001483:Base Sequence; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010766:Phosphorylation; D016133:Polymerase Chain Reaction / Q000379:methods; D011494:Protein Kinases / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D013950:Thymus Gland / Q000201:enzymology / Q000276:immunology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D007527:Isoenzymes; D009838:Oligodeoxyribonucleotides; D011948:Receptors, Antigen, T-Cell; D000001:Calcimycin; D015759:Ionomycin; D004492:Edetic Acid; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium