Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling

Eric Sebzda; Madelon Bracke; Tamara Tugal; Nancy Hogg; Doreen Ann Cantrell

doi:10.1038/ni765

Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling

Eric Sebzda, Madelon Bracke, Tamara Tugal, Nancy Hogg, Doreen Ann Cantrell

Research output: Contribution to journal › Article › peer-review

250 Citations (Scopus)

Abstract

T cell receptor (TCR) stimulation activates the small GTPase Rap1A, which is reported to antagonize Ras signaling and induces T cell anergy. To address its role in vivo, we generated transgenic mice that constitutively expressed active Rap1A within the T cell lineage. We found that active Rap1A did not interfere with the Ras signaling pathway or antagonize T cell activation. Instead of anergy, the T lymphocytes that constitutively expressed active Rap1A showed enhanced TCR-mediated responses, both in thymocytes and mature T cells. In addition, Rap1A activation was sufficient to induce strong activation of the 1 and 2 integrins via an avidity-modulation mechanism. This shows that, far from playing an inhibitory role during T cell activation, Rap1A positively influences T cells by augmenting lymphocyte responses and directing integrin activation.

Original language	English
Pages (from-to)	251-258
Number of pages	8
Journal	Nature Immunology
Volume	3
Issue number	3
DOIs	https://doi.org/10.1038/ni765
Publication status	Published - 2002

Keywords

T lymphocytes

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title = "Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling",

abstract = "T cell receptor (TCR) stimulation activates the small GTPase Rap1A, which is reported to antagonize Ras signaling and induces T cell anergy. To address its role in vivo, we generated transgenic mice that constitutively expressed active Rap1A within the T cell lineage. We found that active Rap1A did not interfere with the Ras signaling pathway or antagonize T cell activation. Instead of anergy, the T lymphocytes that constitutively expressed active Rap1A showed enhanced TCR-mediated responses, both in thymocytes and mature T cells. In addition, Rap1A activation was sufficient to induce strong activation of the 1 and 2 integrins via an avidity-modulation mechanism. This shows that, far from playing an inhibitory role during T cell activation, Rap1A positively influences T cells by augmenting lymphocyte responses and directing integrin activation.",

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author = "Eric Sebzda and Madelon Bracke and Tamara Tugal and Nancy Hogg and Cantrell, \{Doreen Ann\}",

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T1 - Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling

AU - Sebzda, Eric

AU - Bracke, Madelon

AU - Tugal, Tamara

AU - Hogg, Nancy

AU - Cantrell, Doreen Ann

N1 - dc.publisher: Nature Publishing Group

PY - 2002

Y1 - 2002

N2 - T cell receptor (TCR) stimulation activates the small GTPase Rap1A, which is reported to antagonize Ras signaling and induces T cell anergy. To address its role in vivo, we generated transgenic mice that constitutively expressed active Rap1A within the T cell lineage. We found that active Rap1A did not interfere with the Ras signaling pathway or antagonize T cell activation. Instead of anergy, the T lymphocytes that constitutively expressed active Rap1A showed enhanced TCR-mediated responses, both in thymocytes and mature T cells. In addition, Rap1A activation was sufficient to induce strong activation of the 1 and 2 integrins via an avidity-modulation mechanism. This shows that, far from playing an inhibitory role during T cell activation, Rap1A positively influences T cells by augmenting lymphocyte responses and directing integrin activation.

AB - T cell receptor (TCR) stimulation activates the small GTPase Rap1A, which is reported to antagonize Ras signaling and induces T cell anergy. To address its role in vivo, we generated transgenic mice that constitutively expressed active Rap1A within the T cell lineage. We found that active Rap1A did not interfere with the Ras signaling pathway or antagonize T cell activation. Instead of anergy, the T lymphocytes that constitutively expressed active Rap1A showed enhanced TCR-mediated responses, both in thymocytes and mature T cells. In addition, Rap1A activation was sufficient to induce strong activation of the 1 and 2 integrins via an avidity-modulation mechanism. This shows that, far from playing an inhibitory role during T cell activation, Rap1A positively influences T cells by augmenting lymphocyte responses and directing integrin activation.

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SN - 1529-2908

VL - 3

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JO - Nature Immunology

JF - Nature Immunology

IS - 3

ER -

Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling

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