Serum and glucocorticoid-regulated kinase Sgk1 inhibits insulin-dependent activation of phosphomannomutase 2 in transfected COS-7 cells.
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.
Menniti
Miranda
M
Dipartimento di Medicina Sperimentale e Clinica G. Salvatore, Università Magna Graecia, Catanzaro, Italy.
Iuliano
Rodolfo
R
Amato
Rosario
R
Boito
Rosalia
R
Corea
Monica
M
Le Pera
Ilaria
I
Gulletta
Elio
E
Fuiano
Giorgio
G
Perrotti
Nicola
N
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
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