Sci. Signal., 19 February 2013
Conformational Kinase ActivationLck is a tyrosine kinase that is critical for T cell activation, and its activity is induced by the T cell receptor (TCR). Phosphorylation of Lck at various residues either promotes or inhibits its activity, and Lck exists in various phosphorylated states in a T cell. With fluorescence lifetime imaging microscopic analysis of live human T cells and biochemical analyses, Stirnweiss et al. found that TCR activation produced a conformational change in Lck. In vitro studies showed that this "open" conformation of Lck exhibited enhanced kinase activity. Thus, phosphorylation, location, and conformation all potentially contribute to the regulation of Lck activity.
Citation: A. Stirnweiss, R. Hartig, S. Gieseler, J. A. Lindquist, P. Reichardt, L. Philipsen, L. Simeoni, M. Poltorak, C. Merten, W. Zuschratter, Y. Prokazov, W. Paster, H. Stockinger, T. Harder, M. Gunzer, B. Schraven, T Cell Activation Results in Conformational Changes in the Src Family Kinase Lck to Induce Its Activation. Sci. Signal. 6, ra13 (2013).
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