Abstract
The present study has explored T cell antigen receptor-regulated serine kinases in human T cells. The results identify two phosphatidylinositol 3-kinase (PI3K)-controlled serine kinases operating downstream of the T cell receptor (TCR) in primary T cells: (i) protein kinase B whose activation regulates the phosphorylation of glycogen synthase kinase 3 and (ii) ribosomal S6 kinase 1, a kinase with a critical role in the regulation of protein synthesis and cell growth. T cells express two isoforms of S6k1: a 70 kDa cytoplasmic kinase and an 85 kDa isoform that has a classic nuclear localisation. TCR ligation triggers a parallel engagement of both the 70 and 85 kDa isoforms of S6k1 in a response that requires PI3K function.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies / pharmacology
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cells, Cultured
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Chromones / pharmacology
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Enzyme Activation / drug effects
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Glycogen Synthase Kinase 3
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Glycogen Synthase Kinases
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Humans
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Molecular Weight
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Morpholines / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation / drug effects
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Phosphoserine / metabolism
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Receptors, Antigen, T-Cell / metabolism*
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Ribosomal Protein S6 Kinases / chemistry
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Ribosomal Protein S6 Kinases / metabolism*
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Signal Transduction / drug effects
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Sirolimus / pharmacology
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T-Lymphocytes / drug effects
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T-Lymphocytes / enzymology*
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T-Lymphocytes / metabolism*
Substances
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Antibodies
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Chromones
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Morpholines
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Phosphoinositide-3 Kinase Inhibitors
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Proto-Oncogene Proteins
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Receptors, Antigen, T-Cell
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Phosphoserine
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Glycogen Synthase Kinases
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Ribosomal Protein S6 Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Glycogen Synthase Kinase 3
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Sirolimus