PKCdelta inhibits PKCalpha-mediated activation of phospholipase D1 in a manner independent of its protein kinase activity.
The regulation of phospholipase D1 (PLD1) by protein kinase C (PKC) isoforms was analyzed in human melanoma cell lines. 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced PLD1 activation was suppressed by the introduction of PKCdelta as well as its kinase-negative mutant in MeWo cells, which contain PKCalpha but lack PKCbeta. PLD activity was not affected by PKCdelta in G361 cells, which have PKCbeta but are deficient in PKCalpha. In MeWo cells introduced by PKCalpha and PLD1, the association of these proteins was observed, which was enhanced by the TPA treatment. In cells overexpressing PKCdelta in addition to PKCalpha and PLD1, TPA treatment increased the association of PKCdelta and PLD1, while it attenuated the association of PKCalpha and PLD1. These results indicate that PKCdelta inhibits TPA-induced PLD1 activation mediated by PKCalpha through the association with PLD1.
Oka
Masahiro
M
Department of Dermatology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. oka@med.kobe-u.ac.jp
Okada
Taro
T
Nakamura
Shun-ichi
S
Ohba
Motoi
M
Kuroki
Toshio
T
Kikkawa
Ushio
U
Nagai
Hiroshi
H
Ichihashi
Masamitsu
M
Nishigori
Chikako
C
D045744:Cell Line, Tumor; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D010739:Phospholipase D / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects; D011493:Protein Kinase C / Q000502:physiology*; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D011494:Protein Kinases / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016228:Endothelial Growth Factors; D011494:Protein Kinases; C496628:PRKCA protein, human; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D010739:Phospholipase D; C106801:phospholipase D1; D013755:Tetradecanoylphorbol Acetate