Interleukin-1 beta activates c-jun NH2-terminal kinase subgroup of mitogen-activated protein kinases in mesangial cells.
We investigated whether JNK is activated by interleukin-1 beta (IL-1 beta) in mesangial cells. We performed in-gel kinase assays with His-c-jun-(1-79), which contains the amino-terminal activation domain of c-jun and a mutant His-c-jun in which Ser-63 and Ser-73 of His-c-jun were mutated to Ala as the substrates. JNK1 (p45) and JNK2 (p54) isoforms phosphorylated His-c-jun in mesangial cells. IL-1 beta produced a time- and concentration-dependent increase in JNK activity. IL-1 beta did not phosphorylated the mutant, His-c-jun. The IL-1 beta-activated JNK activity was independent of serum and suppressed by neither tyrosine kinase inhibitors nor protein kinase C inhibitors. JNK was also stimulated by anisomycin and okadaic acid but not by phorbol 12-myristate 13-acetate. The protein synthesis inhibitors and okadaic acid potentiated the IL-1 beta-induced JNK activity. Together, these studies indicate that the novel JNK group of protein kinases may play an important role in the signal transduction pathway initiated by proinflammatory cytokines, such as IL-1 beta in mesangial cells.
Guan
Z
Z
Department of Molecular Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Tetsuka
T
T
Baier
L D
LD
Morrison
A R
AR
D000818:Animals; D001769:Blood; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D020928:Mitogen-Activated Protein Kinases; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
D007375:Interleukin-1; D011500:Protein Synthesis Inhibitors; D011994:Recombinant Proteins; D019319:Okadaic Acid; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases