Different beta-subunits determine G-protein interaction with transmembrane receptors.
Regulatory GTP-binding proteins (G proteins) are membrane-attached heterotrimers (alpha, beta, gamma) that mediate cellular responses to a wide variety of extracellular stimuli. They undergo a cycle of guanine-nucleotide exchange and GTP hydrolysis, during which they dissociate into alpha-subunit and beta gamma complex. The roles of G-protein alpha-subunits in these processes and for the specificity of signal transduction are largely established; the beta- and gamma-subunits are essential for receptor-induced G-protein activation and seem to be less diverse and less specific. Although the complementary DNAs for several beta-subunits have been cloned, isolated subunits have only been studied as beta gamma complexes. Functional differences have been ascribed to the gamma-subunit on the basis of extensive sequence similarity among beta-subunits and apparent heterogeneity in gamma-subunit sequences. Beta gamma complexes can interact directly or indirectly with different effectors. They seem to be interchangeable in their interaction with pertussis toxin-sensitive alpha-subunits, so we tested this by microinjecting antisense oligonucleotides into nuclei of a rat pituitary cell line to suppress the synthesis of individual beta-subunits selectively. Here we show that two out of four subtypes of beta-subunits tested (beta 1 and beta 3) are selectively involved in the signal transduction cascades from muscarinic M4 (ref. 4) and somatostatin receptors, respectively, to voltage-dependent Ca2+ channels.
Kleuss
C
C
Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Germany.
Scherübl
H
H
Hescheler
J
J
Schultz
G
G
Wittig
B
B
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology*; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000502:physiology; D017481:Receptors, Somatostatin; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D015220:Calcium Channels; D046911:Macromolecular Substances; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D019204:GTP-Binding Proteins; D002118:Calcium