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PMID: 9584193 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A conserved p38 mitogen-activated protein kinase pathway regulates Drosophila immunity gene expression.

Molecular and cellular biology ·Vol. 18 ·No. 6 ·1998-06-00 ·Pages 3527-39

Han ZS, Enslen H, Hu X, Meng X, Wu IH, Barrett T, Davis RJ, Ip YT

Abstract

Accumulating evidence suggests that the insect and mammalian innate immune response is mediated by homologous regulatory components. Proinflammatory cytokines and bacterial lipopolysaccharide stimulate mammalian immunity by activating transcription factors such as NF-kappaB and AP-1. One of the responses evoked by these stimuli is the initiation of a kinase cascade that leads to the phosphorylation of p38 mitogen-activated protein (MAP) kinase on Thr and Tyr within the motif Thr-Gly-Tyr, which is located within subdomain VIII. We have investigated the possible involvement of the p38 MAP kinase pathway in the Drosophila immune response. Two genes that are highly homologous to the mammalian p38 MAP kinase were molecularly cloned and characterized. Furthermore, genes that encode two novel Drosophila MAP kinase kinases, D-MKK3 and D-MKK4, were identified. D-MKK3 is an efficient activator of both Drosophila p38 MAP kinases, while D-MKK4 is an activator of D-JNK but not D-p38. These data establish that Drosophila indeed possesses a conserved p38 MAP kinase signaling pathway. We have examined the role of the D-p38 MAP kinases in the regulation of insect immunity. The results revealed that one of the functions of D-p38 is to attenuate antimicrobial peptide gene expression following exposure to lipopolysaccharide.

MeSH Terms
Amino Acid Sequence Animals Animals, Genetically Modified Anti-Bacterial Agents/metabolism Anti-Inflammatory Agents/pharmacology Base Sequence Calcium-Calmodulin-Dependent Protein Kinases/genetics,metabolism,physiology Cloning, Molecular Conserved Sequence Drosophila/genetics,immunology Drosophila Proteins Enzyme Inhibitors/pharmacology Gene Expression Regulation Imidazoles/pharmacology Immunity/genetics Insect Proteins/biosynthesis,genetics MAP Kinase Kinase 3 Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinases Molecular Sequence Data Protein Serine-Threonine Kinases/genetics,metabolism Protein-Tyrosine Kinases/genetics,metabolism Pyridines/pharmacology p38 Mitogen-Activated Protein Kinases
Chemicals
Anti-Bacterial Agents Anti-Inflammatory Agents AttA protein, Drosophila AttB protein, Drosophila AttC protein, Drosophila Drosophila Proteins Enzyme Inhibitors Imidazoles Insect Proteins Pyridines attacin antibacterial protein, insect Protein-Tyrosine Kinases Protein Serine-Threonine Kinases Calcium-Calmodulin-Dependent Protein Kinases Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases MAP Kinase Kinase 3 Mitogen-Activated Protein Kinase Kinases SB 203580
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Han Z S
Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Worcester, Massachusetts 01605, USA.
Enslen H
Hu X
Meng X
Wu I H
Barrett T
Davis R J
Ip Y T
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.6.3527
Published
1998-06-00
Pages
3527-39
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC108934
Subset
IM
Grants
NCI NIH HHS · CA65861 · United States
NIGMS NIH HHS · GM53269 · United States
Databases
GENBANK
AF035546, AF035547, AF035548, AF035549, AF035550, AF035551, AF035552
External Links
PubMed source DOI: 10.1128/MCB.18.6.3527 PMC Full Text View journal details
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