title: Modulation of intracellular Ca(2+) via alpha(1B)-adrenoreceptor signaling molecules, G alpha(h) (transglutaminase II) and phospholipase C-delta 1.
abstract: We characterized the alpha(1B)-adrenoreceptor (alpha(1B)-AR)-mediated intracellular Ca(2+) signaling involving G alpha(h) (transglutaminase II, TGII) and phospholipase C (PLC)-delta 1 using DDT1-MF2 cell. Expression of wild-type TGII and a TGII mutant lacking transglutaminase activity resulted in significant increases in a rapid peak and a sustained level of intracellular Ca(2+) concentration ([Ca(2+)](i)) in response to activation of the alpha(1B)-AR. Expression of a TGII mutant lacking the interaction with the receptor or PLC-delta 1 substantially reduced both the peak and sustained levels of [Ca(2+)](i). Expression of TGII mutants lacking the interaction with PLC-delta 1 resulted in a reduced capacitative Ca(2+) entry. Reduced expression of PLC-delta 1 displayed a transient elevation of [Ca(2+)](i) and a reduction in capacitative Ca(2+) entry. Expression of the C2-domain of PLC-delta 1, which contains the TGII interaction site, resulted in reduction of the alpha(1B)-AR-evoked peak increase in [Ca(2+)](i), while the sustained elevation in [Ca(2+)](i) and capacitative Ca(2+) entry remained unchanged. These findings demonstrate that stimulation of PLC-delta 1 via coupling of the alpha(1B)-AR with TGII evokes both Ca(2+) release and capacitative Ca(2+) entry and that capacitative Ca(2+) entry is mediated by the interaction of TGII with PLC-delta 1.
authors.affiliation: Department of Molecular Cardiology, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Sung Koo
authors.initials: SK
authors.lastname: Kang
authors.forename: Dae Kyong
authors.initials: DK
authors.lastname: Kim
authors.forename: Derek S
authors.initials: DS
authors.lastname: Damron
authors.forename: Kwang Jin
authors.initials: KJ
authors.lastname: Baek
authors.forename: Mie-Jae
authors.initials: MJ
authors.lastname: Im
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D016296:Mutagenesis; D054803:Phospholipase C delta; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D010738:Type C Phospholipases; D054803:Phospholipase C delta; D019204:GTP-Binding Proteins; D002118:Calcium