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Positive and negative regulation of JNK1 by protein kinase C and p42 MAP kinase in adult rat hepatocytes
Author(s) -
Jarvis W.David,
Auer Kelly L,
Spector Mark,
Kunos George,
Grant Steven,
Hylemon Philip,
Mikkelsen Ross,
Dent Paul
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00705-9
Subject(s) - chelerythrine , protein kinase c , sphingosine , map kinase kinase kinase , microbiology and biotechnology , mitogen activated protein kinase 3 , biology , mitogen activated protein kinase kinase , ask1 , propidium iodide , map2k7 , kinase , mapk14 , mitogen activated protein kinase , protein kinase a , apoptosis , programmed cell death , cyclin dependent kinase 2 , biochemistry , receptor
The role of protein kinase C (PKC) and p42 MAP kinase signaling in the regulation of proliferation and apoptosis was investigated in freshly isolated and primary cultured rat hepatocytes. Acute treatment of freshly isolated hepatocytes with phenylephrine and EGF caused rapid phasic activations of p42 MAP kinase and JNK1. Acute pre‐treatment of hepatocytes with the PKC inhibitors sphingosine, chelerythrine and bis ‐indolylmaleimide abolished the ability of phenylephrine, but not EGF, to activate p42 MAP kinase and JNK1. Acute pre‐treatments with all of the PKC inhibitors alone increased JNK1 basal activity ∼2‐fold. Acute treatments of primary cultures of hepatocytes with an inhibitor of MEK1 activation (PD98059) also caused inhibition of p42 MAP kinase and a ∼2‐fold activation of JNK1. These data demonstrate that PKC can function as both a proximal activator and a distal inhibitor of signaling through the JNK1/SAP kinase pathway. Treatments (4 h) of primary cultured hepatocytes with sphingosine, chelerythrine, bis ‐indolylmaleimide and PD98059 did not induce apoptosis as judged by propidium iodide staining. Similar acute treatments of HepG2 cells rapidly induced cell death. These data demonstrate that acute inhibition of either PKC or p42 MAP kinase function is sufficient to rapidly induce apoptosis in transformed, but not in non‐transformed hepatocytes.