Inhibition of protein kinase C delta has negative effect on anchorage-independent growth of BCR-ABL-transformed Rat1 cells.
The BCR-ABL oncoprotein transmits transformation signals mainly through pathways involving Ras, Myc and PI3 kinase. Here we report that inhibition of protein kinase C (PKC) delta had negative influence on anchorage-independent growth of Rat1 cells transformed by BCR-ABL. The effect was observed with delta isoform-specific inhibitor rottlerin, but not with Go6976 that inhibits only conventional isoforms. The kinase activity of delta isoform was found to be roughly two-fold higher in BCR-ABL-expressing Rat1 cells than that in mock. Although overexpression of wild type PKC delta did not enhance soft agar colony number by BCR-ABL-transformed Rat1 cells, that of dominant-negative delta isoform reduced it by approximately 40%.
Kin
Y
Y
Department of Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108, Tokyo, Japan.
Shibuya
M
M
Maru
Y
Y
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000494:pharmacology*; D016147:Genes, Tumor Suppressor / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology; D051745:Protein Kinase C-delta; D051381:Rats
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; C015482:protein kinase modulator; C497260:Prkcd protein, rat; D016044:Fusion Proteins, bcr-abl; D011493:Protein Kinase C; D051745:Protein Kinase C-delta