| First Author | Dorn A | Year | 2012 |
| Journal | Cell Immunol | Volume | 276 |
| Issue | 1-2 | Pages | 187-95 |
| PubMed ID | 22695258 | Mgi Jnum | J:188357 |
| Mgi Id | MGI:5440368 | Doi | 10.1016/j.cellimm.2012.05.008 |
| Citation | Dorn A, et al. (2012) Rap1a deficiency modifies cytokine responses and MAPK-signaling in vitro and impairs the in vivo inflammatory response. Cell Immunol 276(1-2):187-95 |
| abstractText | 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-GTP is thought to activate ERK in a ras-independent manner by binding b-raf. Generally, T cells do not express b-raf while they express the adaptor protein raf-1, which is usually sequestered by rap1 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. |
