title: Serum and glucocorticoid-regulated kinase Sgk1 inhibits insulin-dependent activation of phosphomannomutase 2 in transfected COS-7 cells.
abstract: Serum- and glucocorticoid-regulated kinase (Sgk1) is considered to be an essential convergence point for peptide and steroid regulation of ENaC-mediated sodium transport. We tried to identify molecular partners of Sgk1 by yeast two-hybrid screening. Yeast two-hybrid screening showed a specific interaction between Sgk1 and phosphomannomutase (PMM)2, the latter of which is an enzyme involved in the regulation of glycoprotein biosynthesis. The interaction was confirmed in intact cells by coimmunoprecipitation and colocalization detected using confocal microscopy. We were then able to demonstrate that Sgk1 phosphorylated PMM2 in an in vitro assay. In addition, we found that the enzymatic activity of PMM2 is upregulated by insulin treatment and that Sgk1 completely inhibits PMM2 activity both in the absence and in the presence of insulin stimulation. These data provide evidence suggesting that Sgk1 may modulate insulin action on the cotranslational glycosylation of glycoproteins.
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica G. Salvatore, Università Magna Graecia, Catanzaro, Italy.
authors.forename: Miranda
authors.initials: M
authors.lastname: Menniti
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Iuliano
authors.forename: Rosario
authors.initials: R
authors.lastname: Amato
authors.forename: Rosalia
authors.initials: R
authors.lastname: Boito
authors.forename: Monica
authors.initials: M
authors.lastname: Corea
authors.forename: Ilaria
authors.initials: I
authors.lastname: Le Pera
authors.forename: Elio
authors.initials: E
authors.lastname: Gulletta
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fuiano
authors.forename: Nicola
authors.initials: N
authors.lastname: Perrotti
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D005938:Glucocorticoids / Q000378:metabolism; D006031:Glycosylation; D007004:Hypoglycemic Agents / Q000378:metabolism* / Q000494:pharmacology; D017874:Immediate-Early Proteins; D047468:Immunoprecipitation; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017875:Phosphotransferases (Phosphomutases) / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques; D015003:Yeasts; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D001798:Blood Proteins; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D017874:Immediate-Early Proteins; D007328:Insulin; D009687:Nuclear Proteins; D017875:Phosphotransferases (Phosphomutases); D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; C052799:phosphomannomutase