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J Biol Chem. 2000 Jan 21;275(3):2071-9.

Lipopolysaccharide-activated kinase, an essential component for the induction of the antimicrobial peptide genes in Drosophila melanogaster cells.

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  • 1Laboratory of Immunology, Medical Research Center, College of Medicine, Yonsei University, Shinchon-Dong 134, Seoul, South Korea.

Abstract

Eukaryotic organisms use a similar Rel/NF-kappaB signaling cascade for the induction of innate immune genes. In Drosophila, lipopolysaccharide (LPS) signal-induced activation of the Rel/NF-kappaB family transcription factors is an essential step in the transcriptional activation of inducible antimicrobial peptide genes. However, the mechanism by which the LPS-induced signaling pathway proceeds remains largely unknown. Here we have cloned a novel Drosophila LPS-activated kinase (DLAK) that is structurally related to mammalian IkappaB kinases. DLAK is expressed and transiently activated in LPS-responsive Drosophila cells following LPS stimulation. Furthermore, DLAK can interact with Cactus, a Drosophila IkappaB and phosphorylate recombinant Cactus, in vitro. Overexpression of dominant-negative mutant DLAK (DLAK(K50A)) blocks LPS-induced Cactus degradation. DLAK-bound Cactus can be degraded in a LPS signal-dependent fashion, whereas the DLAK(K50A) mutant-bound Cactus is completely resistant to degradation in the presence of LPS. The DLAK(K50A) mutant also inhibits nuclear kappaB binding activity and kappaB-dependent diptericin reporter gene activity in a dose-dependent manner, but the kappaB-dependent diptericin reporter gene activity can be rescued by overexpression of wild type DLAK. Moreover, mRNA analysis of various kappaB-dependent antimicrobial peptide genes shows that LPS inducibility of these genes is greatly impaired in cells overexpressing DLAK(K50A). These results establish that DLAK is a novel LPS-activated kinase, which is an essential signaling component for the induction of antimicrobial peptide genes following LPS treatment in Drosophila cells.

PMID:
10636911
[PubMed - indexed for MEDLINE]
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