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Signal transduction

Rhapsody in G proteins

Nature volume 400, pages 820–821 (1999)Cite this article

Guanine-nucleotide-binding (G) proteins are molecular switches that regulate a variety of cellular processes, transducing the signals received at a cell's surface to elicit a proper biological response from the proteins inside. They come in two flavours — the heterotrimeric G proteins and the small GTPases — and both can be regulated in two ways. The first involves the guanine-nucleotide-exchange factors (GEFs), which induce formation of the GTP-bound (active) form of the G protein. The second invokes the G proteins' intrinsic GTPase activity, which, by hydrolysing GTP to GDP, induces an inactive conformation. This hydrolysing activity can be greatly enhanced by GTPase-activating proteins (GAPs).

Mochizuki et al.1 (on page 891of this issue) and Jordan et al.2 (in the Journal of Biological Chemistry) now describe an unexpected mechanism by which heterotrimeric G proteins can regulate a small GTPase called Rap1. Heterotrimeric G proteins consist of α, β and γ subunits. In the inactive form, this trimeric complex is bound to a so-called seven-pass membrane receptor (or serpentine receptor) on the cell surface. When the receptor is stimulated, GDP is exchanged for GTP. The activated G protein then breaks free from the receptor, and the Gα subunit dissociates from the Gβγ heterodimer. The new studies show that α-subunits of heterotrimeric G proteins directly associate with a GAP for Rap1, resulting in modulation of Rap1 and the extracellular-signal-regulated kinase (ERK).

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Figure 1: Positive and negative regulation of Rap1 by various heterotrimeric guanine-nucleotide-binding (G) proteins.

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Authors and Affiliations

  1. Laboratory for Physiological Chemistry, Utrecht University, Universiteitsweg 100, NL-3584 CG, Utrecht, The Netherlands

    Johannes L. Bos & Fried J. T. Zwartkruis

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  1. Johannes L. Bos
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  2. Fried J. T. Zwartkruis
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Bos, J., Zwartkruis, F. Rhapsody in G proteins. Nature 400, 820–821 (1999). https://doi.org/10.1038/23594

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