Author(s): Dorn A, Zoellner A, Follo M, Martin S, Weber F, et al.
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.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/22695258
Author(s): Kitayama H, Matsuzaki T, Ikawa Y, Noda M
Author(s): Sebzda E, Bracke M, TugalT
Author(s): Duchniewicz M, Zwartkruis T, Kolanczyk M
Author(s): Minato N, Katagiri.K, Hattori M
Author(s): Chrzanowska-Wodnicka M, Gale D, White GC, Vansluys J
Author(s): Carmona G, Göttig S, Orlandi A, Scheele J, Bäuerle T, et al
Author(s): Chen Y, Yu M, Podd A, Wen R, Chrzanowska-Wodnicka M, et al.
Author(s): Li Y, Yan J, De P, Chang HC, Yamauchi A, et al.
Author(s): Jang MW, Yun SP, Park JH,Ryu JM, Lee JH, et al.
Author(s): Yan J, Ingram DA, Qilliam LA
Author(s): Hitchcock IS, Kaushansky K
Author(s): Awasthi A, Samarakoon A, Chu H,Kamalakannan R, Quilliam LA, et al.
Author(s): Ghandour H, Cullere X, Alvarez A , Luscinskas FW, Mayadas TN
Author(s): Shimonaka M, Nakayama T, Fujita N, Katagiri K, Tsuruo T, et al.
Author(s): Satyanarayana A, Gudmundsson KO, Chen X, Coppola V, Tessarollo L, et al.
Author(s): Carmona G, Chavakis E, Koehl U, Zeiher AM, Dimmeler S
Author(s): Molina-Ortiz P, Polizzi S, Ramery E, Gayral S, Delierneux C, et al.
Author(s): Karp JM, LengTeo GS
Author(s): Thankamony SP, Sackstein R
Author(s): Chen CP, Huang JP, Chu TY, Aplin JD, Chen CY, et al.
Author(s): Antignano F, Burrows K, Hughes MR, Han JM, Kron KJ, et al.
Author(s): Zhang X, Cook PC, Zindy E, Williams CJ, Jowitt TA, et al.
Author(s): Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, et al.
Author(s): Zhang T, Termanis A, Özkan B, Bao XX, Culley J, et al.