The post-translational modification of ras p21 is important for Raf-1 activation
- PMID: 8051091
The post-translational modification of ras p21 is important for Raf-1 activation
Abstract
Raf-1, a serine/threonine kinase, is required for the mitogenic action of ras p21. It has been recently demonstrated that ras p21 directly associates with Raf-1. The C-terminal region of ras p21 is modified by farnesylation and carboxyl methylation. This modification is necessary for ras p21 function. To elucidate the role of post-translational modification of ras p21 in Raf-1 activation, we examined ras p21-dependent Raf-1 activity in baculovirus/Sf9 cells overexpressing Raf-1 and ras p21. Coexpression of Raf-1 with v-ras p21 in Sf9 cells stimulated the autophosphorylating activity of Raf-1. The activity of Raf-1, as assessed by its ability to activate extracellular signal-regulated kinase kinase (MEK) in vitro, was also increased when Raf-1 was coexpressed with v-ras p21. However, neither the autophosphorylating activity of Raf-1 nor its ability to activate MEK was stimulated by v-ras p21 mutants which are not post-translationally modified. Raf-1 formed a complex with v-ras p21 and the v-ras p21 mutants in Sf9 cells. These results indicate that the post-translational modification of ras p21 is necessary for Raf-1 activation but that the association of Raf-1 with ras p21 is not sufficient to activate Raf-1.
Similar articles
-
Raf-1 and p21v-ras cooperate in the activation of mitogen-activated protein kinase.Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5772-6. doi: 10.1073/pnas.90.12.5772. Proc Natl Acad Sci U S A. 1993. PMID: 8390681 Free PMC article.
-
Reconstitution of the Raf-1-MEK-ERK signal transduction pathway in vitro.Mol Cell Biol. 1993 Nov;13(11):6615-20. doi: 10.1128/mcb.13.11.6615-6620.1993. Mol Cell Biol. 1993. PMID: 8413257 Free PMC article.
-
Post-translational modification of H-Ras is required for activation of, but not for association with, B-Raf.J Biol Chem. 1996 Mar 1;271(9):4671-8. doi: 10.1074/jbc.271.9.4671. J Biol Chem. 1996. PMID: 8617731
-
Raf meets Ras: completing the framework of a signal transduction pathway.Trends Biochem Sci. 1994 Jul;19(7):279-83. doi: 10.1016/0968-0004(94)90005-1. Trends Biochem Sci. 1994. PMID: 8048167 Review.
-
Interactions between Ras and Raf: key regulatory proteins in cellular transformation.Mol Reprod Dev. 1995 Dec;42(4):493-9. doi: 10.1002/mrd.1080420418. Mol Reprod Dev. 1995. PMID: 8607981 Review.
Cited by
-
Regulation of inducible nitric oxide synthase gene in glial cells.Antioxid Redox Signal. 2006 May-Jun;8(5-6):929-47. doi: 10.1089/ars.2006.8.929. Antioxid Redox Signal. 2006. PMID: 16771683 Free PMC article. Review.
-
Exposure to oxidized low-density lipoprotein reduces activable Ras protein in vascular endothelial cells.In Vitro Cell Dev Biol Anim. 2002 Jun;38(6):320-5. doi: 10.1290/1071-2690(2002)038<0320:ETOLDL>2.0.CO;2. In Vitro Cell Dev Biol Anim. 2002. PMID: 12513119
-
Biology, pathology, and therapeutic targeting of RAS.Adv Cancer Res. 2020;148:69-146. doi: 10.1016/bs.acr.2020.05.002. Epub 2020 Jul 9. Adv Cancer Res. 2020. PMID: 32723567 Free PMC article. Review.
-
Sodium benzoate, a metabolite of cinnamon and a food additive, reduces microglial and astroglial inflammatory responses.J Immunol. 2009 Nov 1;183(9):5917-27. doi: 10.4049/jimmunol.0803336. Epub 2009 Oct 7. J Immunol. 2009. PMID: 19812204 Free PMC article.
-
Polycomb-group complex 1 acts as an E3 ubiquitin ligase for Geminin to sustain hematopoietic stem cell activity.Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10396-401. doi: 10.1073/pnas.0800672105. Epub 2008 Jul 23. Proc Natl Acad Sci U S A. 2008. PMID: 18650381 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
