Constitutive activation of TCR signaling molecules in IL-2-independent Herpesvirus saimiri-transformed T cells.
Both human T cell leukemia virus type I and simian Herpesvirus saimiri (HVS) transform human T cells in vitro. Although IL-2-independent growth in human T cell leukemia virus type I-transformed T cells is associated with constitutive phosphorylation of JAK/STAT kinases, we now demonstrate that different mechanisms may be responsible for the ability of HVS-transformed T cells to proliferate in the absence of exogenous cytokines. The IL-2 independence of an HVS-transformed cell line correlated with constitutive activation of protein tyrosine kinases known to be induced following TCR engagement. Thus, in these cells we observed increased phosphotransferase activity of Lck as well as constitutive tyrosine phosphorylation of the TCR-associated ZAP-70 kinase and expression of the related Syk protein tyrosine kinase. While Syk is generally not expressed in activated T cells, its introduction has been shown to enhance TCR responsiveness. These results suggest that distinct signal transduction cascades can participate in the transition of T cells to IL-2 independence.
Noraz
N
N
Institut de Génétique Moléculaire de Montpellier, France.
Saha
K
K
Ottones
F
F
Smith
S
S
Taylor
N
N
D002455:Cell Division / Q000276:immunology; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000378:metabolism; D006567:Herpesvirus 2, Saimiriine / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D053616:Janus Kinase 3; D019169:Jurkat Cells; D015458:Leukemia, T-Cell; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D014407:Tumor Cells, Cultured; D051746:ZAP-70 Protein-Tyrosine Kinase
D004792:Enzyme Precursors; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C000606896:SYK protein, human; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human