Interleukin-1[beta] activates the c-jun amino-terminal kinase
subgroup of mitogen-activated protein kinases in mesangial cells.
Guan, Zhonghong, Toshifumi Tetsuka, Lisa D. Baier, and Aubrey R.
Morrison.
Departments of Molecular Biology and Pharmacology and Medicine,
Washington University School of Medicine, St Louis, MO
APStracts 2:0190F, 1995.
We investigated whether JNK is activated by 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 phosphorylate 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 (PMA). 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 pro-inflammatory cytokines such as
IL-1[beta] in mesangial cells.
Received 21 August 1995; accepted in final form 19 October 1995.
APS Manuscript Number F279-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95