| Structural highlights
Disease
GRP1_HUMAN Disease susceptibility is associated with variations affecting the gene represented in this entry. Aberrantly spliced isoforms and/or diminished levels of RASGRP1 are found in a cohort of SLE patients raising the possibility that dysregulation of this signaling protein contributes to the development of autoimmunity in a subset of SLE patients.
Function
GRP1_HUMAN Functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. Activates the Erk/MAP kinase cascade. Couples T-lymphocytes and B-lymphocytes antigen receptors to the activation of Ras. Hence, regulates T-cells and B-cells development, homeostasis and differentiation. Functions also in FcERI-evoked degranulation and cytokine secretion by mast cells, regulating allergic responses. May also function in other cell types differentiation.[1] [2] [3] [4] [5] [6] [7]
References
- ↑ Ebinu JO, Stang SL, Teixeira C, Bottorff DA, Hooton J, Blumberg PM, Barry M, Bleakley RC, Ostergaard HL, Stone JC. RasGRP links T-cell receptor signaling to Ras. Blood. 2000 May 15;95(10):3199-203. PMID:10807788
- ↑ Caloca MJ, Zugaza JL, Matallanas D, Crespo P, Bustelo XR. Vav mediates Ras stimulation by direct activation of the GDP/GTP exchange factor Ras GRP1. EMBO J. 2003 Jul 1;22(13):3326-36. PMID:12839994 doi:10.1093/emboj/cdg316
- ↑ Caloca MJ, Zugaza JL, Bustelo XR. Exchange factors of the RasGRP family mediate Ras activation in the Golgi. J Biol Chem. 2003 Aug 29;278(35):33465-73. Epub 2003 Jun 2. PMID:12782630 doi:10.1074/jbc.M302807200
- ↑ Bivona TG, Perez De Castro I, Ahearn IM, Grana TM, Chiu VK, Lockyer PJ, Cullen PJ, Pellicer A, Cox AD, Philips MR. Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1. Nature. 2003 Aug 7;424(6949):694-8. Epub 2003 Jun 29. PMID:12845332 doi:10.1038/nature01806
- ↑ Perez de Castro I, Bivona TG, Philips MR, Pellicer A. Ras activation in Jurkat T cells following low-grade stimulation of the T-cell receptor is specific to N-Ras and occurs only on the Golgi apparatus. Mol Cell Biol. 2004 Apr;24(8):3485-96. PMID:15060167
- ↑ Zugaza JL, Caloca MJ, Bustelo XR. Inverted signaling hierarchy between RAS and RAC in T-lymphocytes. Oncogene. 2004 Jul 29;23(34):5823-33. PMID:15184873 doi:10.1038/sj.onc.1207768
- ↑ Roose JP, Mollenauer M, Gupta VA, Stone J, Weiss A. A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells. Mol Cell Biol. 2005 Jun;25(11):4426-41. PMID:15899849 doi:25/11/4426
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