title: Different roles of protein kinase C-betaI and -delta in the regulation of adipocyte differentiation.
abstract: Protein kinase C (PKC) is a member of serine/threonine protein kinase family that plays important roles in the control of vast variety of cellular functions. Nevertheless, the regulatory effect of PKC on adipogenesis remained not well understood. In this study, we investigated the effect of several PKC isoforms on the adipogenic conversion of 3T3-L1 preadipocytes induced by dexamethasone, isobutylmethylxanthine and insulin. Treatment of cells with broad-spectrum PKC inhibitor Rö318220 suppressed the adipogenesis. Gö6976, a selective inhibitor for PKC isoforms-alpha, -betaI and -mu, also inhibited the adipogenesis of cells. Pretreatment of cells with peroxisomal proliferator activated receptor-gamma (PPARgamma) agonist troglitazone abolished the inhibitory effect of Gö6976 on adipogenesis. The plasmic membrane translocation of PKC-betaI was observed at the first 2 days of differentiation. Whereas no translocation of PKC-alpha and -mu was observed. Overexpression of dominant negative PKC-betaI, but not wild-type PKC-betaI, blocked adipogenesis. This effect of dominant negative PKC-betaI can be reversed by troglitazone, suggesting that PKC-betaI is required for the initiation of adipogenesis. In addition, rottlerin, a specific inhibitor of PKC-delta, can reverse the suppression of adipogenesis mediated by 12-O-tetradecanoyl-phorbol-13-acetate, transforming growth factor-beta1, and epidermal growth factor. These data suggest that PKC-betaI is important in the induction of adipogenesis, while the PKC-delta has an inhibitory role for adipogenesis.
authors.affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Zhou
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
authors.forename: Jianguo
authors.initials: J
authors.lastname: Song
mesh_terms: D041721:3T3-L1 Cells; D000098:Acetophenones / Q000494:pharmacology; D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002454:Cell Differentiation; D002462:Cell Membrane / Q000201:enzymology; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005799:Genes, Dominant / Q000235:genetics; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D000077288:Troglitazone
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; D002227:Carbazoles; D002839:Chromans; D007211:Indoles; D050505:Mutant Proteins; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; C081021:Go 6976; D004815:Epidermal Growth Factor; C085746:rottlerin; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta; D000077288:Troglitazone; D013755:Tetradecanoylphorbol Acetate; C064758:Ro 31-8220