The T cell antigen receptor activates phosphatidylinositol 3-kinase-regulated serine kinases protein kinase B and ribosomal S6 kinase 1.
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.
Lafont
V
V
Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, London, UK. vlafont@crit.univ-montp2.fr
Astoul
E
E
Laurence
A
A
Liautard
J
J
Cantrell
D
D
D000906:Antibodies / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D008970:Molecular Weight; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*
D000906:Antibodies; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002867:Chromones; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010768:Phosphoserine; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011948:Receptors, Antigen, T-Cell; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one