Prolactin and known modulators of rat splenocytes activate nuclear protein kinase C.
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.
Russell
D H
DH
Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, Tampa 33612.
Zorn
N E
NE
Buckley
A R
AR
Crowe
P D
PD
Sauro
M D
MD
Hadden
E M
EM
Farese
R V
RV
Laird
H E
HE
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
D003524:Cyclosporins; D007546:Isoquinolines; D010743:Phospholipids; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011388:Prolactin; D011494:Protein Kinases; D013110:Sphingosine; D005990:Glycerol