The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 occurs via a distinct mechanism than other receptor systems

Michaela Collins; Mikaela Tremblay; Nicole Chapman; Miranda Curtiss; Paul B Rothman; Jon C D Houtman

doi:10.1189/jlb.0409227

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The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 occurs via a distinct mechanism than other receptor systems

Journal article

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Peer reviewed

The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 occurs via a distinct mechanism than other receptor systems

Michaela Collins, Mikaela Tremblay, Nicole Chapman, Miranda Curtiss, Paul B Rothman and Jon C D Houtman

Journal of leukocyte biology, Vol.87(4), pp.691-701

04/2010

DOI: 10.1189/jlb.0409227

PMID: 20028775

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Abstract

The tyrosine kinase Pyk2 is vital for integrating receptor-mediated signals controlling adhesion and motility in neuronal, epithelial, and hematopoietic cell types. In T cells, the stimulation of the TCR and costimulatory, chemokine, cytokine, and integrin receptors leads to the phosphorylation of Pyk2 and the induction of its catalytic activity. However, our understanding of the mechanism of the TCR-induced, site-specific phosphorylation of this kinase is incomplete and contradictory. To address this issue, the role of individual signaling pathways in the phosphorylation of Pyk2 tyrosines 402 and 580 upon TCR activation was assessed in human T cells. In contrast to other receptor systems, the TCR-induced phosphorylation of Pyk2 tyrosines 402 and 580 was dependent on the Src family kinases, Fyn or Lck. Interestingly, the TCR-mediated phosphorylation of Pyk2 tyrosines 402 and 580 did not require Ca(2+) influx, ZAP-70 activation, actin cytoskeleton rearrangement, or PI3K function. These observations are different than other receptor systems, which require the induction of one or more of these pathways. Together, these data have defined more fully the mechanism for the TCR-induced phosphorylation of specific sites on Pyk2, suggesting that the TCR has a distinct pathway for the activation of Pyk2 compared with other receptor systems.

Receptors, Antigen, T-Cell - metabolism

T-Lymphocytes - enzymology

Calcium - metabolism

Jurkat Cells

Humans

Calcium - immunology

Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - immunology

Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - metabolism

Tyrosine - immunology

Enzyme Activation - immunology

Cell Adhesion - immunology

Tyrosine - metabolism

Proto-Oncogene Proteins c-fyn - metabolism

Focal Adhesion Kinase 2 - metabolism

ZAP-70 Protein-Tyrosine Kinase - immunology

ZAP-70 Protein-Tyrosine Kinase - metabolism

Proto-Oncogene Proteins c-fyn - immunology

Receptors, Antigen, T-Cell - immunology

T-Lymphocytes - immunology

Phosphorylation - immunology

Focal Adhesion Kinase 2 - immunology

Details

Title: Subtitle: The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 occurs via a distinct mechanism than other receptor systems
Creators: Michaela Collins - Department of Microbiology, Carver College of Medicine, University of Iowa, 2210 MERF, Iowa City, IA 52242, USA
Mikaela Tremblay
Nicole Chapman
Miranda Curtiss
Paul B Rothman
Jon C D Houtman
Resource Type: Journal article
Publication Details: Journal of leukocyte biology, Vol.87(4), pp.691-701
DOI: 10.1189/jlb.0409227
PMID: 20028775
ISSN: 0741-5400
eISSN: 1938-3673
Grant note: DOI: 10.13039/100000048, name: American Cancer Society; DOI: 10.13039/100011343, name: Holden Comprehensive Cancer Center; DOI: 10.13039/100000968, name: American Heart Association
Language: English
Date published: 04/2010
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984094311902771

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