Characterization of phorbol esters activity on individual mammalian protein kinase C isoforms, using the yeast phenotypic assay

• Type: Article in International Scientific Journal
• Date: 2004

Authors

Saraiva, L (Author) FFUP; Fresco, P (Author) FFUP; Pinto, E (Author) FFUP; Goncalves, J (Author) FFUP

Journal

Title: European Journal of Pharmacology

Vol. 491

Pages: 101-110

ISSN: 0014-2999

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 23 Citations

Scopus - 27 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-000-AE5

DOI: 10.1016/j.ejphar.2004.03.035

Abstract (EN): Ail alternative in vivo assay, based on growth inhibition of yeast expressing an individual mammalian protein kinase C (PKC) isoform (proportional to the degree of PKC activation), was used to characterize the activities of phorbol-12-myristate-13-acetate (PMA) and its analogues on classical (alpha and betaI) novel (delta and eta) and atypical (zeta) PKC isoforms. Effects of PMA, 4alpha-PMA, phorbol-12-myristate-13-acetate-4-O-methyl-ether (MPMA), phorbol-12-monomyristate (PMM), phorbol-12,13-diacetate (PDA), phorbol-13-monoacetate (PA), phorbot-12,13-dibutyrate (PDB), phorbol-12,13-didecanoate (PDD)and 12-deoxyphorbol-13-phenylacetate-20-acetate (dPPA), on growth of yeast expressing individual PKC isoforms was determined. PMA-induced growth inhibition on all isoforms tested (except on PKC-zeta). PDD and PDB presented an efficacy similar to PMA; the other PMA-analogues presented lower efficacies. MPMA and 4alpha-PMA stimulated growth of yeast expressing classical PKCs and reduced the PMA-induced growth inhibition, effects similar to those exhibited by the PKC inhibitors chelerythrine and R-2,6-diamino-N-[[1-(1-oxotridecyl)-2-piperidinyl]methyl]-hexanamide dihydrochloride (NPC 15437). This study reveals that phorbol esters differ on their potency to activate a given PKC isoform, and presents their isoform-selectivity. Furthermore, MPMA and 4alpha-PMA caused effects similar to those expected from PKC inhibition.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10