This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dudek, S. M. Articles by Garcia, J. G.N. Search for Related Content PubMed PubMed Citation Articles by Dudek, S. M. Articles by Garcia, J. G.N. Related Collections Cell signalling/signal transduction Gene expression Oxidant stress

(Circulation Research. 2003;93:794.)
© 2003 American Heart Association, Inc.

Editorials

Rho Family of Guanine Exchange Factors (GEFs) in Cellular Activation

Who’s Dancing? And With Whom?

Steven M. Dudek, Joe G.N. Garcia

From the Johns Hopkins Division of Pulmonary and Critical Care Medicine, Baltimore, Md.

Correspondence to Joe G.N. Garcia, MD, Johns Hopkins Division of Pulmonary and Critical Care Medicine, 1830 Monument St, Room 527, Baltimore, MD 21205. E-mail drgarcia@jhmi.edu

Key Words: Rho • Rac • guanine exchange factor • lysophosphatidic acid

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Over the past decade, an increasing appreciation has developed for the role of small GTP-binding proteins (GTPases) as critical molecular switches. Small GTPases function as important regulators of multiple cellular processes by transducing signals from extracellular stimuli to intracellular effector pathways. The three primary members of the Rho family of GTPases include Rho, Rac, and Cdc42, whose collective activation is most closely linked to actin cytoskeletal rearrangement (see review¹). Classically, Rho activation promotes the assembly of contractile actomyosin stress fibers, Rac activation produces lamellipodia and membrane ruffles, and Cdc42 induces filopodia formation. Because they regulate essential cellular processes such as cell shape, migration, transcription, vesicle trafficking, and barrier function, these proteins represent important potential targets for therapeutic intervention in a diverse array of human diseases. As a result, Rho GTPase regulatory pathways have been the focus of intensive investigation.

Rho GTPases are inactive when GDP-bound and active when GTP-bound. Cycling between these states is controlled by three known classes of regulatory proteins: GTPase-activating proteins (GAPs), guanine nucleotide dissociation inhibitors (GDIs), and guanine nucleotide exchange factors (GEFs). GAPs and GDIs negatively regulate Rho GTPase activation by promoting the GDP-bound state. Conversely, activation of the Rho family is directly controlled by the GEFs, which stimulate the exchange of GDP for GTP (see Figure). GEFs work immediately upstream of Rho proteins to provide a direct link between Rho activation and cell-surface receptors for various cytokines, growth factors, adhesion molecules, and G protein–coupled receptors.² A growing number of Rho family GEFs have . . . [Full Text of this Article]