Inhibition of protein kinase C by calphostin C is light-dependent.
Calphostin C, a secondary metabolite of the fungus Cladosporium cladosporioides, inhibits protein kinase C by competing at the binding site for diacylglycerol and phorbol esters. Calphostin C is a polycyclic hydrocarbon with strong absorbance in the visible and ultraviolet ranges. In characterizing the activity of this compound, we unexpectedly found that the inhibition of [3H]phorbol dibutyrate binding was dependent on exposure to light. Ordinary fluorescent light was sufficient for full activation. The inhibition of protein kinase C activity in cell-free systems and intact cells also required light. Light-dependent cytotoxicity was seen at concentrations about 5-fold higher than those inhibiting protein kinase C.
Bruns
R F
RF
Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, IN 46285.
Miller
F D
FD
Merriman
R L
RL
Howbert
J J
JJ
Heath
W F
WF
Kobayashi
E
E
Takahashi
I
I
Tamaoki
T
T
Nakano
H
H
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002294:Carcinoma, Squamous Cell; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D003624:Darkness; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D007700:Kinetics; D008027:Light; D009281:Naphthalenes; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000528:radiation effects; D051381:Rats; D011919:Rats, Inbred Strains
D009281:Naphthalenes; D011083:Polycyclic Compounds; D015240:Phorbol 12,13-Dibutyrate; D066246:ErbB Receptors; D011493:Protein Kinase C; C058819:calphostin C