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Endocrine Reviews 24 (6): 765-781
Copyright © 2003 by The Endocrine Society

Insights into G Protein Structure, Function, and Regulation

Theresa M. Cabrera-Vera, Jurgen Vanhauwe, Tarita O. Thomas, Martina Medkova, Anita Preininger, Maria R. Mazzoni and Heidi E. Hamm

Department of Molecular Pharmacology and Biological Chemistry (T.M.C.-V., J.V., T.O.T., M.M., A.P., H.E.M.), Institute for Neuroscience, Northwestern University, Chicago, Illinois 60611; Department of Molecular Pharmacology (M.R.M., H.E.M.), Vanderbilt University Medical Center, Nashville, Tennessee 37232; and Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnology (M.R.M.), University of Pisa, Pisa, 56057, Italy

Correspondence: Address all correspondence and requests for reprints to: Heidi E. Hamm, Ph.D., Department of Pharmacology, Vanderbilt University Medical Center, 442 Robinson Research Building, 23rd and Pierce Drive, Nashville, Tennessee 37232. E-mail: heidi.hamm{at}mcmail.vanderbilt.edu

In multicellular organisms from Caenorhabditis elegans to Homo sapiens, the maintenance of homeostasis is dependent on the continual flow and processing of information through a complex network of cells. Moreover, in order for the organism to respond to an ever-changing environment, intercellular signals must be transduced, amplified, and ultimately converted to the appropriate physiological response. The resolution of the molecular events underlying signal response and integration forms the basis of the signal transduction field of research. An evolutionarily highly conserved group of molecules known as heterotrimeric guanine nucleotide-binding proteins (G proteins) are key determinants of the specificity and temporal characteristics of many signaling processes and are the topic of this review. Numerous hormones, neurotransmitters, chemokines, local mediators, and sensory stimuli exert their effects on cells by binding to heptahelical membrane receptors coupled to heterotrimeric G proteins. These highly specialized transducers can modulate the activity of multiple signaling pathways leading to diverse biological responses. In vivo, specific combinations of G{alpha}- and Gß{gamma}-subunits are likely required for connecting individual receptors to signaling pathways. The structural determinants of receptor-G protein-effector specificity are not completely understood and, in addition to involving interaction domains of these primary acting proteins, also require the participation of scaffolding and regulatory proteins.




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