ITK

ITK

The nonreceptor tyrosine kinase Itk (interleukin-2 inducible T-cell kinase) is a member of the TEC-kinase family which encompasses Itk, Rlk, Btk, Bmx, and Tec. It is expressed mainly in immune cells such as T cells, mast cells, NK cells, and NKT cells. Alterations in Itk have been associated with human disorders. These include Itk promoter polymorphisms associated with atopy and the expression of an Itk-Syk fusion protein generated by a chromosomal translocation in T-cell lymphomas. Importantly, the implication of Itk in a human primary immunodeficiency has validated its role as a critical regulator of T lymphocyte function. Mice lacking Itk exhibit impaired TH2 cytokine secretion; however, they have increased circulating serum IgE but exhibit few immunological symptoms of allergic airway responses. Additionally, the use of RNA interference studies, kinase-inactive Itk mutants, and Itk small molecule inhibitors demonstrated that efficient uptake of HIV by CD4 + T cells and viral replication requires Itk kinase activity.

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  • PF 06465469
    2110
    PF 06465469
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More About ITK

The nonreceptor tyrosine kinase Itk (interleukin-2 inducible T-cell kinase) is a member of the TEC-kinase family which encompasses Itk, Rlk, Btk, Bmx, and Tec. It is expressed mainly in immune cells such as T cells, mast cells, NK cells, and NKT cells. Alterations in Itk have been associated with human disorders. These include Itk promoter polymorphisms associated with atopy and the expression of an Itk-Syk fusion protein generated by a chromosomal translocation in T-cell lymphomas. Importantly, the implication of Itk in a human primary immunodeficiency has validated its role as a critical regulator of T lymphocyte function[1]. Mice lacking Itk exhibit impaired TH2 cytokine secretion; however, they have increased circulating serum IgE but exhibit few immunological symptoms of allergic airway responses[2]. Additionally, the use of RNA interference studies, kinase-inactive Itk mutants, and Itk small molecule inhibitors demonstrated that efficient uptake of HIV by CD4 + T cells and viral replication requires Itk kinase activity[3].

[1] AH Andreotti et al. T-cell signaling regulated by the Tec family kinase, Itk. Cold Spring Harb Perspect Biol. 2010 Jul;2(7):a002287.
[2] AS Iyer et al. The Tec family kinase, IL-2-inducible T cell kinase, differentially controls mast cell responses. J Immunol. 2008 Jun 15;180(12):7869-77.
[3] JA Readinger et al. Selective targeting of ITK blocks multiple steps of HIV replication. Proc Natl Acad Sci U S A. 2008 May 6;105(18):6684-9.
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