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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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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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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format | Article |
id | doaj.art-91f12bfd1d844e6199f341b92bf45588 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-14T23:26:53Z |
publishDate | 2012-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
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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