Rho GTPases and signaling networks

  1. Linda Van Aelst1,3 and
  2. Crislyn D’Souza-Schorey2
  1. 1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 USA; 2Department of Cell Biology, Washington University School of Medicine, St. Louis, Missouri 63110 USA

This extract was created in the absence of an abstract.

The Rho GTPases form a subgroup of the Ras superfamily of 20- to 30-kD GTP-binding proteins that have been shown to regulate a wide spectrum of cellular functions. These proteins are ubiquitously expressed across the species, from yeast to man. The mammalian Rho-like GTPases comprise at least 10 distinct proteins: RhoA, B, C, D, and E; Rac1 and 2; RacE; Cdc42Hs, and TC10. A comparison of the amino acid sequences of the Rho proteins from various species has revealed that they are conserved in primary structure and are 50%–55% homologous to each other. Like all members of the Ras superfamily, the Rho GTPases function as molecular switches, cycling between an inactive GDP-bound state and an active GTP-bound state. Until recently, members of the Rho subfamily were believed to be involved primarily in the regulation of cytoskeletal organization in response to extracellular growth factors. However, research from a number of laboratories over the past few years has revealed that the Rho GTPases play crucial roles in diverse cellular events such as membrane trafficking, transcriptional regulation, cell growth control, and development. Consequently, a major challenge has been to unravel the underlying molecular mechanisms by which the Rho GTPases mediate these various activities. Many targets of the Rho GTPases have now been identified and further characterization of some of them has provided major insights toward our understanding of Rho GTPase function at the molecular level. This review aims to summarize the general established principles about the Rho GTPases and some of the more recent exciting findings, hinting at novel, unanticipated functions of the Rho GTPases.

Regulators of the Rho GTPases

Like all members of the Ras superfamily, the activity of the Rho GTPases is determined by the ratio of their GTP/GDP-bound forms in the cell (Boguski and McCormick 1993). The ratio of the two forms is regulated by …

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