Rapid activation of protein kinase C in isolated rat liver nuclei by prolactin, a known hepatic mitogen.
Rat liver nuclei pure by enzymatic and electron microscope criteria contain protein kinase C (PKC) that can be activated several hundredfold within 3 min of addition of prolactin or phorbol 12-tetradecanoate 13-acetate. Rat prolactin stimulated PKC maximally at 10(-12) M, whereas ovine prolactin was maximally stimulatory at 10(-10) M. Activation was time and dose dependent, exhibited a biphasic pattern, and was blocked by anti-prolactin antiserum, by PKC inhibitors such as 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) and sphingosine, and by cyclosporine. Moreover, the ability of prolactin to activate nuclear PKC was inhibited totally by a monoclonal antibody to the rat liver prolactin receptor, implicating a prolactin receptor-mediated activation process. Epidermal growth factor (EGF), a liver mitogen, caused a lesser but significant activation of nuclear PKC. However, EGF and suboptimal prolactin were synergistic. Human growth hormone, which has lactogenic properties, stimulated PKC activity, whereas nonlactogenic substances such as ovine growth hormone, insulin, dexamethasone, and 8-bromo-cAMP were inactive. That this may be a general mechanism for prolactin is suggested by the ability of prolactin to stimulate PKC 140-fold in rat splenocyte nuclei. Prolactin has comitogenic properties in lymphocytes.
Buckley
A R
AR
Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, Tampa 33612.
Crowe
P D
PD
Russell
D H
DH
D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology* / Q000648:ultrastructure; D006728:Hormones / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008854:Microscopy, Electron; D008934:Mitogens; D011388:Prolactin / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D006728:Hormones; D008934:Mitogens; D011388:Prolactin; D011493:Protein Kinase C