title: Constitutively active Lck kinase in T cells drives antigen receptor signal transduction.
abstract: T cell antigen receptor (TCR) and coreceptor ligation is thought to initiate signal transduction by inducing activation of the kinase Lck. Here we showed that catalytically active Lck was present in unstimulated naive T cells and thymocytes and was readily detectable in these cells in lymphoid organs. In naive T cells up to approximately 40% of total Lck was constitutively activated, part of which was also phosphorylated on the C-terminal inhibitory site. Formation of activated Lck was independent of TCR and coreceptors but required Lck catalytic activity and its maintenance relied on monitoring by the HSP90-CDC37 chaperone complex to avoid degradation. The amount of activated Lck did not change after TCR and coreceptor engagement; however it determined the extent of TCR-zeta phosphorylation. Our findings suggest a dynamic regulation of Lck activity that can be promptly utilized to initiate T cell activation and have implications for signaling by other immune receptors.
authors.affiliation: T Cell Signaling Laboratory, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Nika
authors.forename: Cristiana
authors.initials: C
authors.lastname: Soldani
authors.forename: Mogjiborahman
authors.initials: M
authors.lastname: Salek
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Paster
authors.forename: Adrian
authors.initials: A
authors.lastname: Gray
authors.forename: Ruth
authors.initials: R
authors.lastname: Etzensperger
authors.forename: Lars
authors.initials: L
authors.lastname: Fugger
authors.forename: Paolo
authors.initials: P
authors.lastname: Polzella
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.forename: Omer
authors.initials: O
authors.lastname: Dushek
authors.forename: Thomas
authors.initials: T
authors.lastname: Höfer
authors.forename: Antonella
authors.initials: A
authors.lastname: Viola
authors.forename: Oreste
authors.initials: O
authors.lastname: Acuto
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008213:Lymphocyte Activation / Q000276:immunology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology* / Q000378:metabolism; D018613:Microscopy, Confocal; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)