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Itk regulates T cell signaling through localization of active Cdc42
Author(s) -
Singleton Kentner L.,
Fowell Deborah J.,
Wuelfing Christoph
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1064.18
Subject(s) - cdc42 , microbiology and biotechnology , intracellular , signal transduction , chemistry , cell , t cell , regulator , tyrosine kinase , cell signaling , biology , immunology , biochemistry , immune system , gene
The tyrosine kinase Itk can regulate actin accumulation at the T cell/APC interface, elevation of the T cell intracellular calcium concentration, and IL‐4 secretion. The cellular mechanism Itk uses to control these diverse functions is unresolved. Here we have identified Itk as a general regulator of the spatiotemporal organization of T cell activation: Itk controls the localization of the TCR, PLCγ, Cdc42, and Actin. Cdc42 localization is of particular interest, as not the cellular activity of Cdc42 but only its localization to the center of the T cell/APC interface was dependent on Itk. This control of the localization of active Cdc42 is a central part of the cellular mechanism of Itk function: Providing active Cdc42 selectively at the center of the T cell/APC interface in Itk‐deficient T cells could restore Itk‐dependent aspects of T cell activation. Providing Cdc42 without such targeting as a means to raise Cdc42 activity in the entire T cell could not. These data are of wider relevance, as they prove that the control of the localization of a signaling intermediate without affecting its activity can be a central part of the regulation of cellular activation. Supported by the NIH.