Role of protein kinase Calpha in melatonin signal transduction.
Melatonin induces nuclear exclusion of the androgen receptor (AR) via activation of protein kinase C (PKC). The specific members of the PKC superfamily involved in AR nuclear exclusion were investigated in prostate cancer PC3 cells stably transfected with the wild-type androgen receptor (PC3-AR). PKCalpha was essentially cytoplasmic whereas PKCbeta and PKCepsilon were essentially membranal, suggesting their constitutive activity in the PC3-AR cells. Melatonin treatment induced membrane association of PKCalpha in a time and dose dependent manner. The PKCalpha and PKCbeta1 specific inhibitor GO6976 and the PKCbeta isoform-specific inhibitor hispidin had no effects on AR localization under basal conditions. However, GO6976 but not hispidin negated the melatonin-mediated nuclear exclusion of the AR. These data indicate that PKCalpha activation is a critical step in AR nuclear exclusion by melatonin. They also imply that PKCalpha-activation is a potentially effective way to control of the AR activity in prostate cancer cells.
Sampson
S R
SR
Faculty of Life Sciences, Gonda-Goldschmied Center, Bar-Ilan University, Ramat-Gan, Tel Aviv, Israel.
Lupowitz
Z
Z
Braiman
L
L
Zisapel
N
N
D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D008297:Male; D008550:Melatonin / Q000502:physiology*; D011471:Prostatic Neoplasms; D051571:Protein Kinase C-alpha / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D051571:Protein Kinase C-alpha; D008550:Melatonin