Direct evidence of cytoplasmic delivery of PKC-alpha, -epsilon and -zeta pseudosubstrate lipopeptides: study of their implication in the induction of apoptosis.
Protein kinases C (PKC) are serine/threonine kinase enzymes involved in the mechanism of cell survival. Their pseudosubstrate sequences are autoinhibitory domains, which maintain the enzyme in an inactive state in the absence of allosteric activators, thus representing an attractive tool for the modulation of different PKC isoforms. Here, we report the use of palmitoylated modified PKC-alpha, -epsilon, and -zeta pseudosubstrate peptides, and determine their intracellular distribution together with their respective PKC isoenzymes. Finally, we propose that the differential distribution of the peptides is correlated with a selective induction of apoptosis and therefore argues for different involvement of PKC isoforms in the anti-apoptotic program.
Thiam
K
K
UMR 8727, Lille II University, Institut de Biologie et Institut Pasteur de Lille, 1 rue du Pr. A. Calmette, P.O. Box 447, 59021, Lille, France. kader.thiam@pasteur-lille.fr
Loing
E
E
Zoukhri
D
D
Rommens
C
C
Hodges
R
R
Dartt
D
D
Verwaerde
C
C
Auriault
C
C
Gras-Masse
H
H
Sergheraert
C
C
D017209:Apoptosis; D001692:Biological Transport; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D010168:Palmitates / Q000737:chemistry; D019308:Palmitic Acid / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D013347:Subcellular Fractions / Q000378:metabolism; D013379:Substrate Specificity; D000099221:Protein Kinase C zeta
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010168:Palmitates; D019308:Palmitic Acid; D010455:Peptides; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D000099221:Protein Kinase C zeta; C496628:PRKCA protein, human; C497255:PRKCE protein, human