title: Corticotropin-releasing hormone activates protein kinase C in an isoenzyme-specific manner.
abstract: Protein kinase C (PKC) has recently emerged as mediator of corticotropin-releasing hormone (CRH) effects. Aim of the present study was to study the effects of CRH on each PKC isoenzyme. As a model we have used the PC12 rat pheochromocytoma cell line, expressing the CRH type 1 receptor (CRHR1). Our data were as follows: (a) CRH-induced rapid phosphorylation of conventional PKCalpha and PKCbeta, accompanied by parallel increase of their concentration within nucleus. (b) CRH suppressed the phosphorylation of novel PKCdelta and PKCtheta;, which remained in the cytosol. (c) CRH-induced transient phosphorylation of atypical PKClambda and had no effect on PKCmu. (d) The effect of CRH on each PKC isoenzyme was blocked by a CRHR1 antagonist. (e) Blockade of conventional PKC phosphorylation inhibited CRH-induced calcium ion mobilization from intracellular stores as well as the CRH-induced apoptosis and Fas ligand production. In conclusion, our findings suggest that CRH via its CRHR1 receptor differentially regulates PKC-isoenzyme phosphorylation, an apparently physiologically relevant effect since blockade of conventional PKC phosphorylation abolished the biological effect of CRH.
authors.affiliation: Department of Clinical Chemistry-Biochemistry, School of Medicine, University of Crete, Heraklion, Crete GR-710 03, Greece.
authors.forename: Erini
authors.initials: E
authors.lastname: Dermitzaki
authors.forename: Christos
authors.initials: C
authors.lastname: Tsatsanis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Charalampopoulos
authors.forename: Ariadne
authors.initials: A
authors.lastname: Androulidaki
authors.forename: Vassiliki-Ismini
authors.initials: VI
authors.lastname: Alexaki
authors.forename: Elias
authors.initials: E
authors.lastname: Castanas
authors.forename: Achille
authors.initials: A
authors.lastname: Gravanis
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Margioris
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D007527:Isoenzymes / Q000378:metabolism*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D018613:Microscopy, Confocal; D016716:PC12 Cells; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D007527:Isoenzymes; D008024:Ligands; D008562:Membrane Glycoproteins; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; D011493:Protein Kinase C