title: Prolactin and known modulators of rat splenocytes activate nuclear protein kinase C.
abstract: Prolactin (PRL) and other trophic factors rapidly activate a nuclear pool(s) of protein kinase C (nPKC) in purified splenocyte nuclei. The PRL also enhanced [2-3H]glycerol incorporation into nuclear mono- and triacylglycerol. An assay was devised which not only probed the ability of the hormone to activate protein kinase C (PKC) but also demonstrated the presence of nuclear substrates. Using this methodology, a biphasic concentration-response curve to PRL was observed. Heterologous species of PRL and various growth factors also activated nPKC. The PRL-induced nPKC stimulation was antagonized by various immunomodulators, G protein-coupling inhibitors, PKC inhibitors, a calmodulin inhibitor, and a peripheral benzodiazepine agonist and antagonist. A monoclonal antibody to PKC, anti-rat PRL antiserum and a monoclonal anti-rat PRL receptor antibody antagonized PRL-induced PKC-dependent nuclear phosphorylation, further implicating nPKC and a PRL receptor-mediated activation process. Nuclear PKC may be a major target for trophic regulation in response to both positive and negative growth signals.
authors.affiliation: Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, Tampa 33612.
authors.forename: D H
authors.initials: DH
authors.lastname: Russell
authors.forename: N E
authors.initials: NE
authors.lastname: Zorn
authors.forename: A R
authors.initials: AR
authors.lastname: Buckley
authors.forename: P D
authors.initials: PD
authors.lastname: Crowe
authors.forename: M D
authors.initials: MD
authors.lastname: Sauro
authors.forename: E M
authors.initials: EM
authors.lastname: Hadden
authors.forename: R V
authors.initials: RV
authors.lastname: Farese
authors.forename: H E
authors.initials: HE
authors.lastname: Laird
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D003524:Cyclosporins / Q000494:pharmacology; D005990:Glycerol / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D050356:Lipid Metabolism; D008297:Male; D008854:Microscopy, Electron; D010743:Phospholipids / Q000378:metabolism; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013110:Sphingosine / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000201:enzymology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D003524:Cyclosporins; D007546:Isoquinolines; D010743:Phospholipids; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011388:Prolactin; D011494:Protein Kinases; D013110:Sphingosine; D005990:Glycerol