Corticotropin-releasing hormone activates protein kinase C in an isoenzyme-specific manner.
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.
Dermitzaki
Erini
E
Department of Clinical Chemistry-Biochemistry, School of Medicine, University of Crete, Heraklion, Crete GR-710 03, Greece.
Tsatsanis
Christos
C
Charalampopoulos
Ioannis
I
Androulidaki
Ariadne
A
Alexaki
Vassiliki-Ismini
VI
Castanas
Elias
E
Gravanis
Achille
A
Margioris
Andrew N
AN
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
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