title: Conformational states of the kinase Lck regulate clustering in early T cell signaling.
abstract: Phosphorylation of the T cell antigen receptor (TCR) by the tyrosine kinase Lck is an essential step in the activation of T cells. Because Lck is constitutively active, spatial organization may regulate TCR signaling. Here we found that Lck distributions on the molecular level were controlled by the conformational states of Lck, with the open, active conformation inducing clustering and the closed, inactive conformation preventing clustering. In contrast, association with lipid domains and protein networks were not sufficient or necessary for Lck clustering. Conformation-driven Lck clustering was highly dynamic, so that TCR triggering resulted in Lck clusters that contained phosphorylated TCRs but excluded the phosphatase CD45. Our data suggest that Lck conformational states represent an intrinsic mechanism for the intermolecular organization of early T cell signaling.
authors.affiliation: Centre for Vascular Research and Australian Centre for Nanomedicine, University of New South Wales, Sydney, Australia.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Rossy
authors.forename: Dylan M
authors.initials: DM
authors.lastname: Owen
authors.forename: David J
authors.initials: DJ
authors.lastname: Williamson
authors.forename: Zhengmin
authors.initials: Z
authors.lastname: Yang
authors.forename: Katharina
authors.initials: K
authors.lastname: Gaus
mesh_terms: D000494:Allosteric Regulation; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D008856:Microscopy, Fluorescence; D050505:Mutant Proteins / Q000235:genetics; D011487:Protein Conformation; D020239:Receptor Cross-Talk; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*; D019076:Transgenes / Q000235:genetics
chemical_list: D050505:Mutant Proteins; D011948:Receptors, Antigen, T-Cell; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)