G(12)/G(13)-mediated signalling in mammalian physiology and disease.
The human genome encodes hundreds of G-protein-coupled receptors. Their intracellular effects, however, are mediated by only four families of heterotrimeric G proteins: G(s), G(i)/G(o), G(q)/G(11) and G(12)/G(13). Progress in the knowledge about the G(12)/G(13) family has somewhat lagged behind because their downstream effectors remained unknown for several years, and tools to specifically interfere with G(12)/G(13)-mediated signalling were, therefore, missing. However, with the identification of G(12)/G(13)-regulated signalling pathways and the recent application of new techniques, such as conditional gene inactivation, RNA interference or expression of inhibitory proteins, new insights into the in vivo functions of this G-protein family have been gained. It has become clear that this pathway regulates cellular proliferation, movement and morphology in many different organs and that it is centrally involved in various diseases including cancer and cardiovascular disorders. Here, we focus on recent progress made in the analyses of the in vivo functions of mammalian G(12)/G(13)-mediated signalling.
Worzfeld
Thomas
T
Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, D-69120 Heidelberg, Germany.
Wettschureck
Nina
N
Offermanns
Stefan
S
D000818:Animals; D004194:Disease / Q000235:genetics; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology; D015539:Platelet Activation / Q000187:drug effects; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
D044365:GTP-Binding Protein alpha Subunits, G12-G13