Positive and negative regulation of JNK1 by protein kinase C and p42MAP kinase in adult rat hepatocytes

FEBS Letters

Dent, Paul³  Grant, Steven¹  Spector, Mark¹  Auer, Kelly L³  Hylemon, Philip²  Jarvis, W.David⁴  Mikkelsen, Ross³  Kunos, George¹ 

[1] Department of Pharmacology and Toxicology, Medical College of Virginia, Richmond, VA 23298-0058, USA;Department of Microbiology and Immunology, Medical College of Virginia, Richmond, VA 23298-0058, USA;Department of Radiation Oncology, Box 980058, Massey Cancer Center, Medical College of Virginia, Richmond, VA 23298-0058, USA;Department of Medicine, Medical College of Virginia, Richmond, VA 23298-0058, USA

关键词: p42MAP kinase;    JNK1;    Protein kinase C;    Sphingosine;    bis-Indolylmaleimide;    Chelerythrine;    PD98059;    MAP kinase;    mitogen-activated protein kinase;    JNK;    c-Jun NH2-terminal kinase;    PKC;    protein kinase C;    SAP kinase;    stress-activated protein kinase;    AR;    adrenergic receptor;    EGF;    epidermal growth factor;   

DOI  :  10.1016/S0014-5793(97)00705-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown