PMID- 10636911
OWN - NLM
STAT- MEDLINE
DCOM- 20000224
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 3
DP  - 2000 Jan 21
TI  - Lipopolysaccharide-activated kinase, an essential component for the induction of 
      the antimicrobial peptide genes in Drosophila melanogaster cells.
PG  - 2071-9
AB  - 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.
FAU - Kim, Y S
AU  - Kim YS
AD  - Laboratory of Immunology, Medical Research Center, College of Medicine, Yonsei 
      University, Shinchon-Dong 134, Seoul, South Korea.
FAU - Han, S J
AU  - Han SJ
FAU - Ryu, J H
AU  - Ryu JH
FAU - Choi, K H
AU  - Choi KH
FAU - Hong, Y S
AU  - Hong YS
FAU - Chung, Y H
AU  - Chung YH
FAU - Perrot, S
AU  - Perrot S
FAU - Raibaud, A
AU  - Raibaud A
FAU - Brey, P T
AU  - Brey PT
FAU - Lee, W J
AU  - Lee WJ
LA  - eng
SI  - GENBANK/AF140766
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Anti-Infective Agents)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphoproteins)
RN  - 149059-01-8 (cact protein, Drosophila)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (IKKbeta protein, Drosophila)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Anti-Infective Agents/*pharmacology
MH  - Cell Line
MH  - Chromosome Mapping
MH  - Cloning, Molecular
MH  - DNA-Binding Proteins/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drosophila Proteins
MH  - Drosophila melanogaster/*enzymology
MH  - Female
MH  - Genes, rel/genetics
MH  - I-kappa B Kinase
MH  - In Situ Hybridization
MH  - Lipopolysaccharides/*metabolism
MH  - Male
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - NF-kappa B/chemistry
MH  - Phosphoproteins/metabolism
MH  - Protein Binding/drug effects
MH  - Protein Serine-Threonine Kinases/chemistry/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Homology, Amino Acid
MH  - Signal Transduction
MH  - Time Factors
MH  - Up-Regulation
EDAT- 2000/01/15 09:00
MHDA- 2000/02/26 09:00
CRDT- 2000/01/15 09:00
PHST- 2000/01/15 09:00 [pubmed]
PHST- 2000/02/26 09:00 [medline]
PHST- 2000/01/15 09:00 [entrez]
AID - S0021-9258(18)31144-X [pii]
AID - 10.1074/jbc.275.3.2071 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Jan 21;275(3):2071-9. doi: 10.1074/jbc.275.3.2071.