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Activation of the Ras superfamily of small GTPases
Author(s) -
Zheng Yi,
Quilliam Lawrence A
Publication year - 2003
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.embor831
Subject(s) - ras superfamily , gtpase , superfamily , microbiology and biotechnology , biology , computational biology , genetics , biochemistry , gene , gtp' , enzyme
The workshop on ‘Exchange Factors’ was held at Instituto Juan March de Estudios e Investigaciones, Madrid, Spain, during November 4–6, 2002. It was organized by Xose R. Bustelo, J. Silvio Gutkind and Piero Crespo.![][1] The Center for International Meetings on Biology workshop on ‘Exchange Factors’ provided an up‐to‐date view of how guanine‐nucleotide‐exchange factors (GEFs) affect the biochemical pathways that regulate the Ras superfamily of small GTPases, and how these molecules function as part of an interrelated network of regulatory proteins that mediate the biological responses of Ras‐like GTPases (Fig. 1). Reflecting the complex nature of GEF functions, the meeting focused on their structure–function relationships, regulation and biological functions. Particular emphasis was placed on a subset of regulators of the Ras and Rho subfamilies that contain catalytic CDC25 homology domains or Dbl homology (DH)/pleckstrin homology (PH) cassettes, respectively (Fig. 2; Quilliam et al ., 2002; Zheng, 2001).Figure 1. A biochemical model for guanine‐nucleotide‐exchange factor activation of Ras‐like GTPases. The cycle between active (GTP‐bound) and inactive (GDP‐bound) Ras proteins is regulated by guanine‐nucleotide‐exchange factors (GEFs) and GTPase‐activating proteins (GAPs). Extracellular signals, conveyed through specific cell‐surface receptors, modulate GEF activity, which in turn regulates the activity of individual Ras GTPases. The active Ras proteins are able to interact with many effectors, leading to diverse biological responses.Figure 2. Many guanine‐nucleotide‐exchange factors are involved in signalling to small GTPases. The multifunctional domain features of the representative guanine‐nucleotide‐exchange factors (GEFs) discussed at the meeting reflect their diverse biochemical modes of regulation (signal convergence and divergence) and biological function. Due to space limitations, only a subset of these is presented here. GEFs that regulate Ras and Rap proteins are aligned according to their CDC25 domains, whereas GEFs that regulate Rho and Rac proteins are aligned on the basis of their Dbl homology (DH) and pleckstrin homology (PH) … [1]: /embed/graphic-1.gif