Insights into G protein structure, function, and regulation.
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 G beta 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.
Cabrera-Vera
Theresa M
TM
Department of Molecular Pharmacology and Biological Chemistry, Institute for Neuroscience, Northwestern University, Chicago, Illinois 60611, USA.
Vanhauwe
Jurgen
J
Thomas
Tarita O
TO
Medkova
Martina
M
Preininger
Anita
A
Mazzoni
Maria R
MR
Hamm
Heidi E
HE
D000818:Animals; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism; D015394:Molecular Structure; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D011506:Proteins; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins