title: Protein phosphorylation involved in the gene expression of the hydrogen sulphide producing enzyme cystathionine γ-lyase in the pancreatic β-cell.
abstract: Cystathionine γ-lyase (CSE) is one of the major enzymes for the production of hydrogen sulphide (H(2)S), a multifunctional gasotransmitter in the pancreatic β-cell. We examined the mechanisms by which glucose induces CSE expression in mouse pancreatic islets and the insulin-secreting cell line MIN6. CSE expression was increased by anti-diabetic sulphonylureas, and decreased by the ATP-sensitive K(+)-channel opener diazoxide and the voltage-dependent Ca(2+) channel blocker nitrendipine. Application of the synthetic inhibitors of protein kinases revealed the involvement of Ca(2+)/calmodulin-dependent protein kinase (CaMK) II and extracellular signal-regulated protein kinase (ERK) in glucose- and thapsigargin-induced CSE expression. The CaMK IIδ knockdown also suppressed CSE expression. Knockdown of the transcription factors Sp1 and Elk1, both of which can be phosphorylated by ERK, blunted CSE expression. By a reporter assay, we found Sp1 may directly and Elk1 may indirectly regulate CSE expression. These findings suggest Ca(2+)-dependent CSE expression may be mediated via protein phosphorylation of Sp1 and Elk1 in pancreatic β-cells.
authors: Department of Pharmacology, Oita University, 1-1 Idaigaoka, Hasama, Oita 879-5593, Japan.
authors: Shigeki
authors: S
authors: Taniguchi
authors: Toshihide
authors: T
authors: Kimura
authors: Tatsuhito
authors: T
authors: Umeki
authors: Yuka
authors: Y
authors: Kimura
authors: Hideo
authors: H
authors: Kimura
authors: Isao
authors: I
authors: Ishii
authors: Norimichi
authors: N
authors: Itoh
authors: Yasuhito
authors: Y
authors: Naito
authors: Hideyuki
authors: H
authors: Yamamoto
authors: Ichiro
authors: I
authors: Niki
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D016329:Sp1 Transcription Factor / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism
chemical_list: C494113:Elk1 protein, mouse; D007004:Hypoglycemic Agents; D007328:Insulin; D047428:Protein Kinase Inhibitors; D016329:Sp1 Transcription Factor; D050807:ets-Domain Protein Elk-1; D019284:Thapsigargin; D014044:Tolbutamide; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D020928:Mitogen-Activated Protein Kinases; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D005947:Glucose; D005905:Glyburide; D006862:Hydrogen Sulfide