Non-catalytic functions of Pyk2 and Fyn regulate late stage adhesion in human T cells

Nicole M Chapman; Ashley N Yoder; Jon C D Houtman

doi:10.1371/journal.pone.0053011

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Non-catalytic functions of Pyk2 and Fyn regulate late stage adhesion in human T cells

Journal article

Open access

Peer reviewed

Non-catalytic functions of Pyk2 and Fyn regulate late stage adhesion in human T cells

Nicole M Chapman, Ashley N Yoder and Jon C D Houtman

PloS one, Vol.7(12), pp.e53011-e53011

2012

DOI: 10.1371/journal.pone.0053011

PMCID: PMC3531412

PMID: 23300847

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Abstract

T cell activation drives the protective immune response against pathogens, but is also critical for the development of pathological diseases in humans. Cytoskeletal changes are required for downstream functions in T cells, including proliferation, cytokine production, migration, spreading, and adhesion. Therefore, investigating the molecular mechanism of cytoskeletal changes is crucial for understanding the induction of T cell-driven immune responses and for developing therapies to treat immune disorders related to aberrant T cell activation. In this study, we used a plate-bound adhesion assay that incorporated near-infrared imaging technology to address how TCR signaling drives human T cell adhesion. Interestingly, we observed that T cells have weak adhesion early after TCR activation and that binding to the plate was significantly enhanced 30-60 minutes after receptor activation. This late stage of adhesion was mediated by actin polymerization but was surprisingly not dependent upon Src family kinase activity. By contrast, the non-catalytic functions of the kinases Fyn and Pyk2 were required for late stage human T cell adhesion. These data reveal a novel TCR-induced signaling pathway that controls cellular adhesion independent of the canonical TCR signaling cascade driven by tyrosine kinase activity.

Cell Line

Humans

Middle Aged

Actins - metabolism

Signal Transduction - immunology

Proto-Oncogene Proteins c-fyn - metabolism

Focal Adhesion Kinase 2 - metabolism

T-Lymphocytes - cytology

T-Lymphocytes - metabolism

Cell Adhesion - physiology

Adolescent

Adult

T-Lymphocytes - immunology

Cell Shape - physiology

Details

Title: Subtitle: Non-catalytic functions of Pyk2 and Fyn regulate late stage adhesion in human T cells
Creators: Nicole M Chapman - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States of America
Ashley N Yoder
Jon C D Houtman
Resource Type: Journal article
Publication Details: PloS one, Vol.7(12), pp.e53011-e53011
DOI: 10.1371/journal.pone.0053011
PMID: 23300847
PMCID: PMC3531412
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Grant note: T32 AI007485 / NIAID NIH HHS R01 CA136729 / NCI NIH HHS
Language: English
Date published: 2012
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984094518102771

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