Diversity and selectivity of receptor-G protein interaction.
Cells in a living organism communicate with each other through extracellular molecules such as hormones, neurotransmitters, and growth factors. The majority of these molecules transmit their signal by interacting with a three-protein transmembrane signal transduction system whose single components interact sequentially and reversibly. Agonist binding to a heptahelical receptor results in activation of heterotrimeric guanine nucleotide-binding proteins (G proteins) that modulate the activity of one or more effector systems. Considering that hundreds of G protein-coupled receptors transduce signals by interacting with a limited repertoire of G proteins, the question of specificity governing the coupling of receptors to G proteins arises. The conceptualization of signal transduction pathways in a linear fashion (one receptor coupling to one G protein that activates one effector) is inadequate to explain experimental results. In the present review, G protein-mediated signal transduction is depicted as a complex signaling network with divergent and convergent pathways at each transduction level, i.e. receptor, G protein, and effector. The recent realization that "classical" signaling pathways appear to be activated in parallel with signaling cascades primarily described for growth factors and cytokines adds an additional level of intriguing complexity.
Gudermann
T
T
Institut für Pharmakologie, Freie Universität Berlin, Germany.
Kalkbrenner
F
F
Schultz
G
G
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D016207:Cytokines; D006133:Growth Substances; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins