title: Serum- and glucocorticoid-induced protein kinase 1 (SGK1) increases the cystic fibrosis transmembrane conductance regulator (CFTR) in airway epithelial cells by phosphorylating Shank2E protein.
abstract: The glucocorticoid dexamethasone increases cystic fibrosis transmembrane conductance regulator (CFTR) abundance in human airway epithelial cells by a mechanism that requires serum- and glucocorticoid-induced protein kinase 1 (SGK1) activity. The goal of this study was to determine whether SGK1 increases CFTR abundance by phosphorylating Shank2E, a PDZ domain protein that contains two SGK1 phosphorylation consensus sites. We found that SGK1 phosphorylates Shank2E as well as a peptide containing the first SGK1 consensus motif of Shank2E. The dexamethasone-induced increase in CFTR abundance was diminished by overexpression of a dominant-negative Shank2E in which the SGK1 phosphorylation sites had been mutated. siRNA-mediated reduction of Shank2E also reduced the dexamethasone-induced increase in CFTR abundance. Taken together, these data demonstrate that the glucocorticoid-induced increase in CFTR abundance requires phosphorylation of Shank2E at an SGK1 consensus site.
authors.affiliation: From the Department of Microbiology and Immunology and Katja.UU.Koeppen@Dartmouth.edu.
authors.forename: Katja
authors.initials: K
authors.lastname: Koeppen
authors.affiliation: From the Department of Microbiology and Immunology and.
authors.forename: Bonita A
authors.initials: BA
authors.lastname: Coutermarsh
authors.affiliation: Department of Biochemistry, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755.
authors.forename: Dean R
authors.initials: DR
authors.lastname: Madden
authors.affiliation: From the Department of Microbiology and Immunology and.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Stanton
mesh_terms: D020816:Amino Acid Motifs; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D020545:Respiratory Mucosa / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; C505032:CFTR protein, human; C122162:SHANK2 protein, human
keywords: ABC Transporter; Chronic Obstructive Pulmonary Disease (COPD); Cystic Fibrosis; Dexamethasone; Glucocorticoid; Membrane Trafficking; Serum- and Glucocorticoid-induced Protein Kinase