title: Heterotrimeric G proteins in the control of parathyroid hormone actions.
abstract: Parathyroid hormone (PTH) is a key regulator of skeletal physiology and calcium and phosphate homeostasis. It acts on bone and kidney to stimulate bone turnover, increase the circulating levels of 1,25 dihydroxyvitamin D and calcium and inhibit the reabsorption of phosphate from the glomerular filtrate. Dysregulated PTH actions contribute to or are the cause of several endocrine disorders. This calciotropic hormone exerts its actions via binding to the PTH/PTH-related peptide receptor (PTH1R), which couples to multiple heterotrimeric G proteins, including Gsand Gq/11Genetic mutations affecting the activity or expression of the alpha-subunit of Gs, encoded by theGNAScomplex locus, are responsible for several human diseases for which the clinical findings result, at least partly, from aberrant PTH signaling. Here, we review the bone and renal actions of PTH with respect to the different signaling pathways downstream of these G proteins, as well as the disorders caused byGNASmutations.
authors.affiliation: Endocrine UnitDepartment of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA bastepe@helix.mgh.harvard.edu.
authors.forename: Murat
authors.initials: M
authors.lastname: Bastepe
authors.affiliation: Department of Pediatric EndocrinologyMarmara University School of Medicine, Istanbul, Turkey.
authors.forename: Serap
authors.initials: S
authors.lastname: Turan
authors.affiliation: Endocrine UnitDepartment of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: He
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002864:Chromogranins / Q000235:genetics* / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D009154:Mutation; D010281:Parathyroid Hormone / Q000235:genetics* / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D002864:Chromogranins; C473449:PTH1R protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D044168:Receptor, Parathyroid Hormone, Type 1; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C406732:GNAS protein, human; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019205:GTP-Binding Protein alpha Subunits, Gs; D002118:Calcium
keywords: G proteins; GNAS; PTH; bone; kidney