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

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 adhes...

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Main Authors: Nicole M Chapman, Ashley N Yoder, Jon C D Houtman
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3531412?pdf=render
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author Nicole M Chapman
Ashley N Yoder
Jon C D Houtman
author_facet Nicole M Chapman
Ashley N Yoder
Jon C D Houtman
author_sort Nicole M Chapman
collection DOAJ
description 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.
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spelling doaj.art-91f12bfd1d844e6199f341b92bf455882022-12-21T22:43:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5301110.1371/journal.pone.0053011Non-catalytic functions of Pyk2 and Fyn regulate late stage adhesion in human T cells.Nicole M ChapmanAshley N YoderJon C D HoutmanT 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.http://europepmc.org/articles/PMC3531412?pdf=render
spellingShingle Nicole M Chapman
Ashley N Yoder
Jon C D Houtman
Non-catalytic functions of Pyk2 and Fyn regulate late stage adhesion in human T cells.
PLoS ONE
title Non-catalytic functions of Pyk2 and Fyn regulate late stage adhesion in human T cells.
title_full Non-catalytic functions of Pyk2 and Fyn regulate late stage adhesion in human T cells.
title_fullStr Non-catalytic functions of Pyk2 and Fyn regulate late stage adhesion in human T cells.
title_full_unstemmed Non-catalytic functions of Pyk2 and Fyn regulate late stage adhesion in human T cells.
title_short Non-catalytic functions of Pyk2 and Fyn regulate late stage adhesion in human T cells.
title_sort non catalytic functions of pyk2 and fyn regulate late stage adhesion in human t cells
url http://europepmc.org/articles/PMC3531412?pdf=render
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AT joncdhoutman noncatalyticfunctionsofpyk2andfynregulatelatestageadhesioninhumantcells