Abstract
We have isolated cDNA clones from a human placental library that code for a low molecular weight GTP-binding protein originally designated Gp (also called G25K). This identification is based on comparisons with the available peptide sequences for the purified human Gp protein and the use of two highly specific anti-peptide antibodies. The predicted amino acid sequence of the protein is very similar to those of various members of the ras superfamily of low molecular weight GTP-binding proteins, including the N-, Ki-, and Ha-ras proteins (30-35% identical), the rho proteins (approximately 50% identical), and the rac proteins (approximately 70% identical). The highest degree of sequence identity (80%) is found with the Saccharomyces cerevisiae cell-division-cycle protein CDC42. The human placental gene, which we designate CDC42Hs, complements the cdc42-1 mutation in S. cerevisiae, which suggests that this GTP-binding protein is the human homolog of the yeast protein.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adams A. E., Johnson D. I., Longnecker R. M., Sloat B. F., Pringle J. R. CDC42 and CDC43, two additional genes involved in budding and the establishment of cell polarity in the yeast Saccharomyces cerevisiae. J Cell Biol. 1990 Jul;111(1):131–142. doi: 10.1083/jcb.111.1.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779–827. doi: 10.1146/annurev.bi.56.070187.004023. [DOI] [PubMed] [Google Scholar]
- Didsbury J., Weber R. F., Bokoch G. M., Evans T., Snyderman R. rac, a novel ras-related family of proteins that are botulinum toxin substrates. J Biol Chem. 1989 Oct 5;264(28):16378–16382. [PubMed] [Google Scholar]
- Evans T., Brown M. L., Fraser E. D., Northup J. K. Purification of the major GTP-binding proteins from human placental membranes. J Biol Chem. 1986 May 25;261(15):7052–7059. [PubMed] [Google Scholar]
- Gallwitz D., Donath C., Sander C. A yeast gene encoding a protein homologous to the human c-has/bas proto-oncogene product. Nature. 1983 Dec 15;306(5944):704–707. doi: 10.1038/306704a0. [DOI] [PubMed] [Google Scholar]
- Hall A. The cellular functions of small GTP-binding proteins. Science. 1990 Aug 10;249(4969):635–640. doi: 10.1126/science.2116664. [DOI] [PubMed] [Google Scholar]
- Hart M. J., Polakis P. G., Evans T., Cerione R. A. The identification and characterization of an epidermal growth factor-stimulated phosphorylation of a specific low molecular weight GTP-binding protein in a reconstituted phospholipid vesicle system. J Biol Chem. 1990 Apr 15;265(11):5990–6001. [PubMed] [Google Scholar]
- Johnson D. I., Pringle J. R. Molecular characterization of CDC42, a Saccharomyces cerevisiae gene involved in the development of cell polarity. J Cell Biol. 1990 Jul;111(1):143–152. doi: 10.1083/jcb.111.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kawata M., Matsui Y., Kondo J., Hishida T., Teranishi Y., Takai Y. A novel small molecular weight GTP-binding protein with the same putative effector domain as the ras proteins in bovine brain membranes. Purification, determination of primary structure, and characterization. J Biol Chem. 1988 Dec 15;263(35):18965–18971. [PubMed] [Google Scholar]
- Kitayama H., Sugimoto Y., Matsuzaki T., Ikawa Y., Noda M. A ras-related gene with transformation suppressor activity. Cell. 1989 Jan 13;56(1):77–84. doi: 10.1016/0092-8674(89)90985-9. [DOI] [PubMed] [Google Scholar]
- Koland J. G., O'Brien K. M., Cerione R. A. Expression of epidermal growth factor receptor sequences as E. coli fusion proteins: applications in the study of tyrosine kinase function. Biochem Biophys Res Commun. 1990 Jan 15;166(1):90–100. doi: 10.1016/0006-291x(90)91915-f. [DOI] [PubMed] [Google Scholar]
- Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
- Madaule P., Axel R. A novel ras-related gene family. Cell. 1985 May;41(1):31–40. doi: 10.1016/0092-8674(85)90058-3. [DOI] [PubMed] [Google Scholar]
- Milburn M. V., Tong L., deVos A. M., Brünger A., Yamaizumi Z., Nishimura S., Kim S. H. Molecular switch for signal transduction: structural differences between active and inactive forms of protooncogenic ras proteins. Science. 1990 Feb 23;247(4945):939–945. doi: 10.1126/science.2406906. [DOI] [PubMed] [Google Scholar]
- Munemitsu S., Innis M. A., Clark R., McCormick F., Ullrich A., Polakis P. Molecular cloning and expression of a G25K cDNA, the human homolog of the yeast cell cycle gene CDC42. Mol Cell Biol. 1990 Nov;10(11):5977–5982. doi: 10.1128/mcb.10.11.5977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pizon V., Chardin P., Lerosey I., Olofsson B., Tavitian A. 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):201–204. [PubMed] [Google Scholar]
- Polakis P. G., Snyderman R., Evans T. Characterization of G25K, a GTP-binding protein containing a novel putative nucleotide binding domain. Biochem Biophys Res Commun. 1989 Apr 14;160(1):25–32. doi: 10.1016/0006-291x(89)91615-x. [DOI] [PubMed] [Google Scholar]
- Polakis P. G., Weber R. F., Nevins B., Didsbury J. R., Evans T., Snyderman R. Identification of the ral and rac1 gene products, low molecular mass GTP-binding proteins from human platelets. J Biol Chem. 1989 Oct 5;264(28):16383–16389. [PubMed] [Google Scholar]
- Rosenberg A. H., Lade B. N., Chui D. S., Lin S. W., Dunn J. J., Studier F. W. Vectors for selective expression of cloned DNAs by T7 RNA polymerase. Gene. 1987;56(1):125–135. doi: 10.1016/0378-1119(87)90165-x. [DOI] [PubMed] [Google Scholar]
- Salminen A., Novick P. J. A ras-like protein is required for a post-Golgi event in yeast secretion. Cell. 1987 May 22;49(4):527–538. doi: 10.1016/0092-8674(87)90455-7. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sewell J. L., Kahn R. A. Sequences of the bovine and yeast ADP-ribosylation factor and comparison to other GTP-binding proteins. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4620–4624. doi: 10.1073/pnas.85.13.4620. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
- Touchot N., Chardin P., Tavitian A. Four additional members of the ras gene superfamily isolated by an oligonucleotide strategy: molecular cloning of YPT-related cDNAs from a rat brain library. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8210–8214. doi: 10.1073/pnas.84.23.8210. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waldo G. L., Evans T., Fraser E. D., Northup J. K., Martin M. W., Harden T. K. Identification and purification from bovine brain of a guanine-nucleotide-binding protein distinct from Gs, Gi and Go. Biochem J. 1987 Sep 1;246(2):431–439. doi: 10.1042/bj2460431. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamamoto K., Kondo J., Hishida T., Teranishi Y., Takai Y. Purification and characterization of a GTP-binding protein with a molecular weight of 20,000 in bovine brain membranes. Identification as the rho gene product. J Biol Chem. 1988 Jul 15;263(20):9926–9932. [PubMed] [Google Scholar]