title: T cell activation results in conformational changes in the Src family kinase Lck to induce its activation.
abstract: The lymphocyte-specific Src family protein tyrosine kinase p56(Lck) (Lck) is essential for T cell development and activation and, hence, for adaptive immune responses. The mechanism by which Lck activity is directed toward specific substrates in response to T cell receptor (TCR) activation remains elusive. We used fluorescence lifetime imaging microscopy to assess the activation-dependent spatiotemporal changes in the conformation of Lck in live human T cells. Kinetic analysis of the fluorescence lifetime of Lck biosensors enabled the direct visualization of the dynamic local opening of 20% of the total amount of Lck proteins after activation of T cells with antibody against CD3 or by superantigen-loaded antigen-presenting cells. Parallel biochemical analysis of TCR complexes revealed that the conformational changes in Lck correlated with the induction of Lck enzymatic activity. These data show the dynamic, local activation through conformational change of Lck at sites of TCR engagement.
authors: Institute of Molecular and Clinical Immunology, Otto von Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors: Anja
authors: A
authors: Stirnweiss
authors: Roland
authors: R
authors: Hartig
authors: Steffi
authors: S
authors: Gieseler
authors: Jonathan A
authors: JA
authors: Lindquist
authors: Peter
authors: P
authors: Reichardt
authors: Lars
authors: L
authors: Philipsen
authors: Luca
authors: L
authors: Simeoni
authors: Mateusz
authors: M
authors: Poltorak
authors: Camilla
authors: C
authors: Merten
authors: Werner
authors: W
authors: Zuschratter
authors: Yury
authors: Y
authors: Prokazov
authors: Wolfgang
authors: W
authors: Paster
authors: Hannes
authors: H
authors: Stockinger
authors: Thomas
authors: T
authors: Harder
authors: Matthias
authors: M
authors: Gunzer
authors: Burkhart
authors: B
authors: Schraven
mesh_terms: D015374:Biosensing Techniques; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000737:chemistry / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)