Differential regulation of human NK cell-mediated cytotoxicity by the tyrosine kinase Itk.

Differential regulation of human NK cell-mediated cytotoxicity by the tyrosine kinase Itk. Research Abstract Details 

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Differential regulation of human NK cell-mediated cytotoxicity by the tyrosine kinase Itk. Abstract Text:

Dianne Khurana,Laura N Arneson,Renee A Schoon,Christopher J Dick,Paul J Leibson,

NK cells are effector lymphocytes that can recognize and eliminate virally infected and transformed cells. NK cells express distinct activating receptors, including an ITAM-containing FcR complex that recognizes Ab-coated targets, and the DNAX-activating protein of 10 kDa-containing NKG2D receptor complex that recognizes stress-induced ligands. The regulatory role of specific tyrosine kinases in these pathways is incompletely understood. In this study, we show that, in activated human NK cells, the tyrosine kinase IL-2-inducible T cell kinase (Itk), differentially regulates distinct NK-activating receptors. Enhanced expression of Itk leads to increases in calcium mobilization, granule release, and cytotoxicity upon stimulation of the ITAM-containing FcR, suggesting that Itk positively regulates FcR-initiated cytotoxicity. In contrast, enhanced Itk expression decreases cytotoxicity and granule release downstream of the DNAX-activating protein of 10 kDa-containing NKG2D receptor, suggesting that Itk is involved in a pathway of negative regulation of NKG2D-initiated granule-mediated killing. Using a kinase mutant, we show that the catalytic activity of Itk is required for both the positive and negative regulation of these pathways. Complementary experiments where Itk expression was suppressed also showed differential regulation of the two pathways. These findings suggest that Itk plays a complex role in regulating the functions initiated by distinct NK cell-activating receptors. Moreover, understanding how these pathways may be differentially regulated has relevance in the setting of autoimmune diseases and antitumor immune responses where NK cells play key regulatory roles.

Differential regulation of human NK cell-mediated cytotoxicity by the tyrosine kinase Itk. Publishing Authors By Initials

D Khurana,LN Arneson,RA Schoon,CJ Dick,PJ Leibson,

For similar proteins: membrane proteins: receptors, cell surface: receptors, immunologic research abstracts see: proteins: membrane proteins: receptors, cell surface: receptors, immunologic research

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Differential regulation of human NK cell-mediated cytotoxicity by the tyrosine kinase Itk. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 178

Page Numbers: 3575-82

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 15

MONTH: Mar

YEAR: 2007

Differential regulation of human NK cell-mediated cytotoxicity by the tyrosine kinase Itk. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985117

Differential regulation of human NK cell-mediated cytotoxicity by the tyrosine kinase Itk. Keywords Mesh Terms:

KEYWORDS: Receptors, Immunologic

MESH TERMS: immunology

Chemical & Substance for Abstract: Differential regulation of human NK cell-mediated cytotoxicity by the tyrosine kinase Itk. Information

Substance Name: emt protein-tyrosine kinase

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for Differential regulation of human NK cell-mediated cytotoxicity by the tyrosine kinase Itk.

AFFILIATION: Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA 47752

ACRONYM: CA

MEDLINETA: J Immunol

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