Home LiteratureArticle Details
PMID: 8094051 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Characterization of a guanine nucleotide dissociation stimulator for a ras-related GTPase.

The EMBO journal ·Vol. 12 ·No. 1 ·1993-01-00 ·Pages 339-47

Albright CF, Giddings BW, Liu J, Vito M, Weinberg RA

Abstract

ras-related GTPases participate in signaling for a variety of cellular processes. The GTPases cycle between a GTP-bound active state and a GDP-bound inactive state. This cycling is partially controlled by guanine nucleotide dissociation stimulators (GDS, also known as exchange factors). We report on the molecular cloning of cDNAs encoding a new mammalian GDS protein, using sequences derived from the yeast ras GDS proteins as probes. The encoded protein stimulates the dissociation of guanine nucleotides from the ras-related ralA and ralB GTPases at a rate at least 30-fold faster than the intrinsic nucleotide dissociation rate. This new GDS, ralGDS, is at least 20-fold more active on the ralA and ralB GTPases than on any other GTPase tested, including other members of the ras family (H-ras, N-ras, K-ras, R-ras, rap1a and rap2), members of the rho family (rhoA, rhoB and CDC42-Hs) and members of the rab family (rab3a and ypt1). While the ralGDS protein is phosphorylated on serine residues, we find no evidence that phosphorylation affects the activity of insect cell-expressed ralGDS towards the ralA or ralB GTPase. The 3600 nucleotide ralGDS mRNA and the 115 kDa protein were found in all tissues and cell lines examined.

Related Genes
CDC42-Hs H-ras K-ras N-ras R-ras rab rab3a ralA ralB ralGDS rap1a rap2 ras rho rhoA rhoB ypt1
MeSH Terms
Amino Acid Sequence Animals Baculoviridae/genetics Base Sequence Blotting, Northern Cell Line Cloning, Molecular Fungal Proteins/genetics,metabolism GTP Phosphohydrolases/genetics,metabolism GTP-Binding Proteins/genetics,metabolism Genetic Vectors Guanosine Diphosphate/metabolism Guanosine Triphosphate/metabolism Insecta Mice Molecular Sequence Data Multigene Family Oligodeoxyribonucleotides Poly A/genetics,isolation & purification Polymerase Chain Reaction RNA, Messenger/genetics,isolation & purification Transfection ral Guanine Nucleotide Exchange Factor rap GTP-Binding Proteins
Chemicals
Fungal Proteins Oligodeoxyribonucleotides RNA, Messenger ral Guanine Nucleotide Exchange Factor Guanosine Diphosphate Poly A Guanosine Triphosphate GTP Phosphohydrolases GTP-Binding Proteins rap GTP-Binding Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Albright C F
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
Giddings B W
Liu J
Vito M
Weinberg R A
References (52)
52 references, click to expand
  1. Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1.
    Nature. 1991 Nov 7;354(6348):80-2 PMID: 1944575
  2. Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase.
    Cell. 1991 Nov 15;67(4):701-16 PMID: 1934068
  3. Both stimulatory and inhibitory GDP/GTP exchange proteins, smg GDS and rho GDI, are active on multiple small GTP-binding proteins.
    Biochem Biophys Res Commun. 1992 Jan 31;182(2):921-30 PMID: 1734890
  4. The Son of sevenless gene product: a putative activator of Ras.
    Science. 1992 Jan 31;255(5044):603-6 PMID: 1736363
  5. The hematopoietically expressed vav proto-oncogene shares homology with the dbl GDP-GTP exchange factor, the bcr gene and a yeast gene (CDC24) involved in cytoskeletal organization.
    Oncogene. 1992 Apr;7(4):611-8 PMID: 1565462
  6. Mutational and kinetic analyses of the GTPase-activating protein (GAP)-p21 interaction: the C-terminal domain of GAP is not sufficient for full activity.
    Mol Cell Biol. 1992 May;12(5):2050-6 PMID: 1569940
  7. Cloning by functional complementation of a mouse cDNA encoding a homologue of CDC25, a Saccharomyces cerevisiae RAS activator.
    EMBO J. 1992 Jun;11(6):2151-7 PMID: 1376246
  8. Regulation of p21ras activity.
    Trends Genet. 1991 Nov-Dec;7(11-12):346-51 PMID: 1820685
  9. Identification of murine homologues of the Drosophila son of sevenless gene: potential activators of ras.
    Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6511-5 PMID: 1631150
  10. RAS residues that are distant from the GDP binding site play a critical role in dissociation factor-stimulated release of GDP.
    EMBO J. 1992 Aug;11(8):2855-62 PMID: 1639059
  11. Molecular cloning of cDNAs encoding a guanine-nucleotide-releasing factor for Ras p21.
    Nature. 1992 Jul 23;358(6384):351-4 PMID: 1379346
  12. Mechanistic aspects of signaling through Ras in NIH 3T3 cells.
    Science. 1992 Jul 31;257(5070):671-4 PMID: 1496380
  13. Association between GTPase activators for Rho and Ras families.
    Nature. 1992 Sep 10;359(6391):153-4 PMID: 1522900
  14. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  15. Organization and reorganization of immunoglobulin genes in A-MULV-transformed cells: rearrangement of heavy but not light chain genes.
    Cell. 1981 Dec;27(2 Pt 1):381-90 PMID: 6277505
  16. A comprehensive set of sequence analysis programs for the VAX.
    Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 PMID: 6546423
  17. High level transient expression of a chloramphenicol acetyl transferase gene by DEAE-dextran mediated DNA transfection coupled with a dimethyl sulfoxide or glycerol shock treatment.
    Nucleic Acids Res. 1984 Jul 25;12(14):5707-17 PMID: 6589587
  18. Characterization, cloning and sequence analysis of the CDC25 gene which controls the cyclic AMP level of Saccharomyces cerevisiae.
    EMBO J. 1986 Feb;5(2):375-80 PMID: 3011405
  19. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis.
    Science. 1986 Oct 17;234(4774):364-8 PMID: 2876518
  20. The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway.
    Cell. 1987 Mar 13;48(5):789-99 PMID: 3545497
  21. CDC25: a component of the RAS-adenylate cyclase pathway in Saccharomyces cerevisiae.
    Science. 1987 Mar 6;235(4793):1218-21 PMID: 3547648
  22. cDNA sequence for human bcr, the gene that translocates to the abl oncogene in chronic myeloid leukaemia.
    EMBO J. 1987 Jan;6(1):115-9 PMID: 3107980
  23. Nucleotide sequence of the CLS4 (CDC24) gene of Saccharomyces cerevisiae.
    Gene. 1987;54(1):125-32 PMID: 3301539
  24. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs.
    Nucleic Acids Res. 1987 Oct 26;15(20):8125-48 PMID: 3313277
  25. The predicted DBL oncogene product defines a distinct class of transforming proteins.
    Proc Natl Acad Sci U S A. 1988 Apr;85(7):2061-5 PMID: 3281159
  26. Expression of the ras-related ralA, rho12 and rab genes in adult mouse tissues.
    Oncogene. 1988 Aug;3(2):231-4 PMID: 2457862
  27. Molecular cloning and characterization of the human dbl proto-oncogene: evidence that its overexpression is sufficient to transform NIH/3T3 cells.
    EMBO J. 1988 Aug;7(8):2465-73 PMID: 3056717
  28. Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: isolation of the MAK16 gene and analysis of an adjacent gene essential for growth at low temperatures.
    Yeast. 1987 Mar;3(1):51-7 PMID: 3332963
  29. N-terminal mutations activate the leukemogenic potential of the myristoylated form of c-abl.
    EMBO J. 1989 Feb;8(2):449-56 PMID: 2542016
  30. Coding sequences of human ralA and ralB cDNAs.
    Nucleic Acids Res. 1989 Jun 12;17(11):4380 PMID: 2662142
  31. The C-terminal part of a gene partially homologous to CDC 25 gene suppresses the cdc25-5 mutation in Saccharomyces cerevisiae.
    Gene. 1989 Apr 15;77(1):21-30 PMID: 2545538
  32. 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):16383-9 PMID: 2550440
  33. Multicopy suppression of the cdc24 budding defect in yeast by CDC42 and three newly identified genes including the ras-related gene RSR1.
    Proc Natl Acad Sci U S A. 1989 Dec;86(24):9976-80 PMID: 2690082
  34. Homologous activators of ras in fission and budding yeast.
    Nature. 1990 Mar 22;344(6264):355-7 PMID: 2107403
  35. A simple, rapid method for the purification of poly A+ RNA.
    Biotechniques. 1988 Feb;6(2):114-6 PMID: 2908499
  36. A cytosolic protein catalyzes the release of GDP from p21ras.
    Science. 1990 Apr 6;248(4951):67-9 PMID: 2181667
  37. The cellular functions of small GTP-binding proteins.
    Science. 1990 Aug 10;249(4969):635-40 PMID: 2116664
  38. Stimulation of p21ras upon T-cell activation.
    Nature. 1990 Aug 23;346(6286):719-23 PMID: 2201921
  39. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  40. The GTPase superfamily: a conserved switch for diverse cell functions.
    Nature. 1990 Nov 8;348(6297):125-32 PMID: 2122258
  41. Modulation of guanine nucleotides bound to Ras in NIH3T3 cells by oncogenes, growth factors, and the GTPase activating protein (GAP).
    J Biol Chem. 1990 Nov 25;265(33):20437-42 PMID: 2122974
  42. SDC25, a CDC25-like gene which contains a RAS-activating domain and is a dispensable gene of Saccharomyces cerevisiae.
    Mol Cell Biol. 1991 Jan;11(1):202-12 PMID: 1986220
  43. The GTPase superfamily: conserved structure and molecular mechanism.
    Nature. 1991 Jan 10;349(6305):117-27 PMID: 1898771
  44. Genetic dissection of a neurodevelopmental pathway: Son of sevenless functions downstream of the sevenless and EGF receptor tyrosine kinases.
    Cell. 1991 Jan 11;64(1):39-48 PMID: 1846090
  45. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe.
    Methods Enzymol. 1991;194:795-823 PMID: 2005825
  46. A workbench for multiple alignment construction and analysis.
    Proteins. 1991;9(3):180-90 PMID: 2006136
  47. Molecular cloning of the cDNA for stimulatory GDP/GTP exchange protein for smg p21s (ras p21-like small GTP-binding proteins) and characterization of stimulatory GDP/GTP exchange protein.
    Mol Cell Biol. 1991 May;11(5):2873-80 PMID: 1901951
  48. Yeast BUD5, encoding a putative GDP-GTP exchange factor, is necessary for bud site selection and interacts with bud formation gene BEM1.
    Cell. 1991 Jun 28;65(7):1213-24 PMID: 1905981
  49. Functional cloning of BUD5, a CDC25-related gene from S. cerevisiae that can suppress a dominant-negative RAS2 mutant.
    Cell. 1991 Jun 28;65(7):1225-31 PMID: 1905982
  50. Overexpression of RPI1, a novel inhibitor of the yeast Ras-cyclic AMP pathway, down-regulates normal but not mutationally activated ras function.
    Mol Cell Biol. 1991 Aug;11(8):3894-904 PMID: 1649384
  51. A stimulatory GDP/GTP exchange protein for smg p21 is active on the post-translationally processed form of c-Ki-ras p21 and rhoA p21.
    Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6442-6 PMID: 1907371
  52. Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product.
    Nature. 1991 Nov 28;354(6351):311-4 PMID: 1956381
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-01-00
Pages
339-47
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413211
Subset
IM
Grants
NCI NIH HHS · 35-CA39826 · United States
NCI NIH HHS · 5T32-CA0941 · United States
Databases
GENBANK
L07924, L07925, L09676, L09677, L09678, L09679, L09680, L09681, L09682, L09683
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2