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

@article{Sebzda2002Rap1APR,
  title={Rap1A positively regulates T cells via integrin activation rather than inhibiting lymphocyte signaling},
  author={Eric Sebzda and Madelon Bracke and Tamara Tugal and Nancy Hogg and Doreen A. Cantrell},
  journal={Nature Immunology},
  year={2002},
  volume={3},
  pages={251-258}
}
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… Expand
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References

SHOWING 1-10 OF 53 REFERENCES
Costimulation through CD28 Suppresses T Cell Receptor-dependent Activation of the Ras-like Small GTPase Rap1 in Human T Lymphocytes*
TLDR
A potential role for Rap1 in T cell receptor signaling is demonstrated and inactivation of Rap1 is suggested as a candidate target of CD28-dependent costimulatory signals required for T cell antigen responsiveness. Expand
CD28 and the Tyrosine Kinase Lck Stimulate Mitogen-Activated Protein Kinase Activity in T Cells via Inhibition of the Small G Protein Rap1
TLDR
It is shown here that TCR-mediated stimulation of MAP kinase extracellular-signal-regulated kinases (ERKs) is limited by activation of the Ras antagonist Rap1, suggesting that CD28-mediated Rap1 GTPase-activating protein activation can help explain the augmentation of ERKs during CD28 costimulation. Expand
Activation of the Rap1 GTPase by the B Cell Antigen Receptor*
TLDR
It is shown that BCR engagement activates Rap1 and that this is dependent on production of diacylglycerol (DAG) by phospholipase C-γ, and the DAG-dependent pathway does not involve Crk signaling complexes since phorbol dibutyrate could activate Rap1 without inducing the formation of these complexes. Expand
The Small Gtpase, Rap1, Mediates Cd31-Induced Integrin Adhesion
TLDR
It is shown that the cytoplasmic tail of CD31, an important integrin adhesion amplifier, propagates signals that induce T cell adhesion via β1 (VLA-4) and β2 (LFA-1) integrins, and identifies the small GTPase, Rap1, as a critical mediator of this effect. Expand
Rap1 GTPase-activating Protein SPA-1 Negatively Regulates Cell Adhesion*
TLDR
It is indicated that Rap1 GTP is required for the cell adhesion induced by both extracellular matrix and soluble factors, which is negatively regulated by SPA-1. Expand
The GTPase Rap1 controls functional activation of macrophage integrin αMβ2 by LPS and other inflammatory mediators
TLDR
In macrophages, the Rap1 GTPase regulates activation of the alphaMbeta2 integrin in response to a wide variety of inflammatory mediators, namely the complement-opsonized phagocytic targets. Expand
Positive Regulation of T Cell Activation and Integrin Adhesion by the Adapter Fyb/Slap
TLDR
Fyb/Slap is the first molecular adapter to be identified that couples TCR stimulation to the avidity modulation of integrins governing T cell adhesion. Expand
Rap1 Is Activated by Erythropoietin or Interleukin-3 and Is Involved in Regulation of β1 Integrin-mediated Hematopoietic Cell Adhesion*
TLDR
The results suggest that Epo and IL-3 activate Rap1 at least partly through the CrkL-C3G complex as well as through additional pathways most likely involving phospholipase Cγ and strongly implicate Rap1 in regulation of β1integrin-mediated hematopoietic cell adhesion. Expand
Raf‐1 provides a dominant but not exclusive signal for the induction of CD69 expression on T cells
TLDR
Raf‐1 was shown to be necessary for PMA‐induced CD69 expression, since transfection of a dominant inhibitory form of Raf‐1 blocked the up‐regulation of CD69 by PMA, and studies with the calcium ionophore ionomycin identified a previously uncharacterized pathway regulating the expression ofCD69 in T cells. Expand
Raf regulates positive selection
TLDR
Raf regulates positive selection in the thymus as evidenced by both reduced numbers of mature thymocytes and a decrease in CD8+ thymocyte numbers in female mice doubly transgenic for DN‐Raf and a class I‐restricted H‐Y TCR. Expand
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5
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