Journal
CELLULAR IMMUNOLOGY
Volume 276, Issue 1-2, Pages 187-195Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2012.05.008
Keywords
Rap1; ras(+); Raf1; CD3(+); PMA; CD3/CD28; Inflammation; Cytokines
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Funding
- Deutsche Forschungsgemeinschaft [Sche-354/8-1]
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Rap1, which is closely related to ras, plays a key role in T-cell receptor (TCR)-signaling. TCR-stimulation without costimulation leads to constitutively activated rap1, which may mediate T-cell anergy via inhibition of ras-dependent induction of extracellular signal-regulated kinases (ERK). This activation is mediated by a second protein kinase b-Raf. Rap1-GIP is thought to activate ERK in a ras-independent manner by binding b-raf. Generally, T cells do not express b-rat while they express the adaptor protein raf-1, which is usually sequestered by rapt leading to inhibition of ras-mediated ERK activation. In this study, we demonstrate that in rap1-deficient T cells, signaling by the ERK and p38 kinases is increased following activation by different stimuli leading to increased intracellular accumulation and secretion of cytokines. In addition, in a hypersensitivity model rap1-deficient mice demonstrated reduced contact dermatitis compared to wildtype mice, demonstrating the impact of rap1-deficiency on the inflammatory response in vivo. (C) 2012 Elsevier Inc. All rights reserved.
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