Post-translational processing and subcellular localization of the Ras-related Rap2 protein
- PMID: 1923507
Post-translational processing and subcellular localization of the Ras-related Rap2 protein
Abstract
The ras-related rap2 gene encodes a 21 kDa GTP-binding protein that exhibits many structural similarities with Ras proteins. In particular, it contains a C-terminal CAAX sequence (C, cysteine; A, aliphatic residue; X, any amino acid) which has been shown to direct the post-translational modifications responsible for membrane binding of Ras proteins and nuclear lamins. We have generated cell lines overexpressing the Rap2 protein as well as specific anti-Rap2 antibodies and show that the protein is tightly associated with cellular membranes. Similarly to Ras proteins, the Rap2 protein is synthesized as a soluble and hydrophilic precursor that is processed to the mature hydrophobic membrane-bound form. During its maturation, the Rap2 protein is modified by the attachment of both palmitate and polyisoprenoid groups, as is also the case for H- and N-Ras proteins. Subcellular fractionation by sucrose density centrifugation as well as indirect immunofluorescence experiments show that the Rap2 protein is localized in a low-density compartment that morphologically overlaps with the endoplasmic reticulum, whereas Ras proteins are associated with the plasma membrane. In spite of similar post-translational modifications by palmitoylation and polyisoprenylation, Ras and Rap2 proteins are thus located on distinct subcellular structures.
Similar articles
-
Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the 'effector' region.Oncogene. 1988 Aug;3(2):201-4. Oncogene. 1988. PMID: 3045729
-
Plasma membrane recruitment of RalGDS is critical for Ras-dependent Ral activation.Oncogene. 1999 Feb 11;18(6):1303-12. doi: 10.1038/sj.onc.1202425. Oncogene. 1999. PMID: 10022812
-
Isoprenoid modification and plasma membrane association: critical factors for ras oncogenicity.Cancer Cells. 1991 Sep;3(9):331-40. Cancer Cells. 1991. PMID: 1751286 Review.
-
Association of rap1 and rap2 proteins with the specific granules of human neutrophils. Translocation to the plasma membrane during cell activation.J Biol Chem. 1992 Mar 25;267(9):6396-402. J Biol Chem. 1992. PMID: 1556142
-
Insider information: how palmitoylation of Ras makes it a signaling double agent.Sci STKE. 2002 Oct 1;2002(152):pe41. doi: 10.1126/stke.2002.152.pe41. Sci STKE. 2002. PMID: 12359913 Review.
Cited by
-
Tracking brain palmitoylation change: predominance of glial change in a mouse model of Huntington's disease.Chem Biol. 2013 Nov 21;20(11):1421-34. doi: 10.1016/j.chembiol.2013.09.018. Epub 2013 Nov 7. Chem Biol. 2013. PMID: 24211138 Free PMC article.
-
Biochemical characterization of RGS14: RGS14 activity towards G-protein alpha subunits is independent of its binding to Rap2A.Biochem J. 2006 Feb 15;394(Pt 1):309-15. doi: 10.1042/BJ20051086. Biochem J. 2006. PMID: 16246175 Free PMC article.
-
MINK and TNIK differentially act on Rap2-mediated signal transduction to regulate neuronal structure and AMPA receptor function.J Neurosci. 2010 Nov 3;30(44):14786-94. doi: 10.1523/JNEUROSCI.4124-10.2010. J Neurosci. 2010. PMID: 21048137 Free PMC article.
-
Rap2 as a slowly responding molecular switch in the Rap1 signaling cascade.Mol Cell Biol. 2000 Aug;20(16):6074-83. doi: 10.1128/MCB.20.16.6074-6083.2000. Mol Cell Biol. 2000. PMID: 10913189 Free PMC article.
-
Biology of the Rap proteins, members of the ras superfamily of GTP-binding proteins.Biochem J. 1993 Jan 1;289 ( Pt 1)(Pt 1):17-24. doi: 10.1042/bj2890017. Biochem J. 1993. PMID: 8424755 Free PMC article. Review. No abstract available.
Publication types
MeSH terms
Substances
LinkOut - more resources
Miscellaneous