A growing family of guanine nucleotide exchange factors is responsible for activation of ras-family GTPases

Lawrence Quilliam, John F. Rebhun, Ariel F. Castro

Research output: Contribution to journalArticle

201 Citations (Scopus)

Abstract

GTPases of the Ras subfamily regulate a diverse array of cellular-signaling pathways, coupling extracellular signals to the intracellular response machinery. Guanine nucleotide exchange factors (GEFs) are primarily responsible for linking cell-surface receptors to Ras protein activation. They do this by catalyzing the dissociation of GDP from the inactive Ras proteins. GTP can then bind and induce a conformational change that permits interaction with downstream effectors. Over the past 5 years, approximately 20 novel Ras-family GEFs have been identified and characterized. These data indicate that a variety of different signaling mechanisms can be induced to activate Ras, enabling tyrosine kinases, G-protein-coupled receptors, adhesion molecules, second messengers, and various protein-interaction modules to relocate and/or activate GEFs and elevate intracellular Ras-GTP levels. This review discusses the structure and function of the catalytic or CDC25 homology domain common to almost all Ras-family GEFs. It also details our current knowledge about the regulation and function of this rapidly growing family of enzymes that include Sosl and 2, GRF1 and 2, CaIDAG-GEF/GRPI-4, C3G, cAMP-GEF/Epac 1 and 2, PDZ-GEFs, MR-GEF, RalGDS family members, RaIGPS, BCAR3, Smg GDS, and phospholipase Cε{lunate}.

Original languageEnglish
Pages (from-to)391-444
Number of pages54
JournalProgress in Nucleic Acid Research and Molecular Biology
Volume71
StatePublished - 2002

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Guanine Nucleotide Exchange Factors
ras Proteins
ras Guanine Nucleotide Exchange Factors
Guanosine Triphosphate
Guanine Nucleotide-Releasing Factor 2
Cell Surface Receptors
Type C Phospholipases
Second Messenger Systems
G-Protein-Coupled Receptors
Protein-Tyrosine Kinases
Enzymes
Proteins

ASJC Scopus subject areas

  • Molecular Biology

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A growing family of guanine nucleotide exchange factors is responsible for activation of ras-family GTPases. / Quilliam, Lawrence; Rebhun, John F.; Castro, Ariel F.

In: Progress in Nucleic Acid Research and Molecular Biology, Vol. 71, 2002, p. 391-444.

Research output: Contribution to journalArticle

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