Proline-rich tyrosine kinase 2 controls PI3-kinase activation downstream of the T cell antigen receptor in human T cells

Nicole M Chapman; Ashley N Yoder; Kathryn M Barbón; Mahmood Y Bilal; Sean F Connolly; Jon C D Houtman

doi:10.1189/jlb.2A1013-568RRR

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Proline-rich tyrosine kinase 2 controls PI3-kinase activation downstream of the T cell antigen receptor in human T cells

Journal article

Open access

Peer reviewed

Proline-rich tyrosine kinase 2 controls PI3-kinase activation downstream of the T cell antigen receptor in human T cells

Nicole M Chapman, Ashley N Yoder, Kathryn M Barbón, Mahmood Y Bilal, Sean F Connolly and Jon C D Houtman

Journal of leukocyte biology, Vol.97(2), pp.285-296

02/2015

DOI: 10.1189/jlb.2A1013-568RRR

PMCID: PMC4304419

PMID: 25387834

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Abstract

TCR-induced signaling controls T cell activation that drives adaptive immunity against infections, but it can also induce dysfunctional T cell responses that promote pathologic disease. The PI3K pathway regulates many downstream effector responses after TCR stimulation. However, the molecular mechanisms that induce PI3K function downstream of the TCR are not fully understood. We have previously shown that Pyk2 is activated downstream of the TCR in a PI3K-independent manner. Although Pyk2 controls adhesion, proliferation, and cytokine production in T cells, the mechanisms by which it controls these processes are not known. In this study, we generated Pyk2-deficient human T cells to elucidate further the role that this kinase plays in TCR-induced effector functions and signaling. We observed that Pyk2 localized with the p85 regulatory subunit of PI3K at the LAT complex and that PI3K-dependent signaling was impaired in Pyk2-deficient T cells. Likewise, functions downstream of PI3K, including IFN-γ production and proliferation, were also suppressed in human T cells deficient in Pyk2. Collectively, these data demonstrate that Pyk2 is a critical regulator of PI3K function downstream of the TCR.

Cell Proliferation

Humans

Male

Class Ia Phosphatidylinositol 3-Kinase - immunology

Enzyme Activation - immunology

Cell Adhesion - immunology

Focal Adhesion Kinase 2 - genetics

T-Lymphocytes - cytology

Interferon-gamma - immunology

Female

Receptors, Antigen, T-Cell - immunology

T-Lymphocytes - immunology

Receptors, Antigen, T-Cell - genetics

Interferon-gamma - genetics

Class Ia Phosphatidylinositol 3-Kinase - genetics

Enzyme Activation - genetics

Focal Adhesion Kinase 2 - immunology

Details

Title: Subtitle: Proline-rich tyrosine kinase 2 controls PI3-kinase activation downstream of the T cell antigen receptor in human T cells
Creators: Nicole M Chapman - Interdisciplinary Graduate Program in Immunology and Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Ashley N Yoder - Interdisciplinary Graduate Program in Immunology and Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Kathryn M Barbón - Interdisciplinary Graduate Program in Immunology and Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Mahmood Y Bilal - Interdisciplinary Graduate Program in Immunology and Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Sean F Connolly - Interdisciplinary Graduate Program in Immunology and Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Jon C D Houtman - Interdisciplinary Graduate Program in Immunology and Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA jon-houtman@uiowa.edu
Resource Type: Journal article
Publication Details: Journal of leukocyte biology, Vol.97(2), pp.285-296
DOI: 10.1189/jlb.2A1013-568RRR
PMID: 25387834
PMCID: PMC4304419
NLM abbreviation: J Leukoc Biol
ISSN: 0741-5400
eISSN: 1938-3673
Grant note: R01-CA136729 / NCI NIH HHS T32 AI007485 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS R01 CA136729 / NCI NIH HHS
Language: English
Date published: 02/2015
Academic Unit: Microbiology and Immunology; Pathology; Internal Medicine
Record Identifier: 9984094343302771

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