title: Signal transduction via G-protein-linked receptors: physiological regulation from the plasma membrane to the genome.
abstract: Many neurotransmitters, hormones, and drugs express their actions through binding to cell-surface receptors that are coupled to membrane-localized effectors via GTP-binding regulatory proteins (G-proteins). Muscarinic acetylcholine, alpha- and beta-adrenergic receptors are members of this populous class of G-protein-linked receptors. Adenylyl cyclase, phospholipase C, and ion channel activities are examples of effectors regulated via these receptors. Signal transduction via G-protein-linked receptors can be regulated at the level of the receptor, G-protein(s), and effector(s). Activation of G-protein-mediated pathway propagates the signal and leads to desensitization (short-term adaptation) and then down-regulation (long-term adaptation). How transmembrane signaling is linked to expression at the level of the gene (transcriptional control), at the level of mRNA (post-transcriptional control) and at the level of the protein (post-translational modification) remains a central question of neurobiology. Investigations at each of these potential loci for regulation have begun to reveal the molecular basis for down-regulation by agonist, up-regulation by permissive hormones (like adrenal steroids), and cross-regulation among G-protein-mediated pathways. The general topic will be discussed drawing upon recent studies of the regulation of the adrenergic receptor family (alpha- and beta-). These recent advances provide a focus for a broader understanding of the integration of information between the genome and transmembrane signaling.
authors.affiliation: Department of Pharmacology, State University of New York, Stony Brook 11794-8651.
authors.forename: C C
authors.initials: CC
authors.lastname: Malbon
authors.forename: M
authors.initials: M
authors.lastname: Berrios
authors.forename: S J
authors.initials: SJ
authors.lastname: Guest
authors.forename: J R
authors.initials: JR
authors.lastname: Hadcock
authors.forename: G M
authors.initials: GM
authors.lastname: Morris
authors.forename: P A
authors.initials: PA
authors.lastname: Galvin-Parton
authors.forename: H Y
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015698:Genomic Library; D006801:Humans; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins