title: Inhibition of protein kinase C by calphostin C is light-dependent.
abstract: 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.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, IN 46285.
authors.forename: R F
authors.initials: RF
authors.lastname: Bruns
authors.forename: F D
authors.initials: FD
authors.lastname: Miller
authors.forename: R L
authors.initials: RL
authors.lastname: Merriman
authors.forename: J J
authors.initials: JJ
authors.lastname: Howbert
authors.forename: W F
authors.initials: WF
authors.lastname: Heath
authors.forename: E
authors.initials: E
authors.lastname: Kobayashi
authors.forename: I
authors.initials: I
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Tamaoki
authors.forename: H
authors.initials: H
authors.lastname: Nakano
mesh_terms: 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
chemical_list: D009281:Naphthalenes; D011083:Polycyclic Compounds; D015240:Phorbol 12,13-Dibutyrate; D066246:ErbB Receptors; D011493:Protein Kinase C; C058819:calphostin C