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Mol Cell Biol, June 1998, p. 3527-3539, Vol. 18, No. 6
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

A Conserved p38 Mitogen-Activated Protein Kinase Pathway Regulates Drosophila Immunity Gene Expression

Zhiqiang Stanley Han,1 Hervé Enslen,1,2 Xiaodi Hu,1 Xiangjun Meng,1 I-Huan Wu,1,2 Tamera Barrett,1,2 Roger J. Davis,1,2 and Y. Tony Ip1,3,*

Program in Molecular Medicine, Department of Biochemistry and Molecular Biology,1 and Department of Cell Biology,3 University of Massachusetts Medical Center, Howard Hughes Medical Institute,2 Worcester, Massachusetts 01605

Received 1 December 1997/Returned for modification 6 February 1998/Accepted 17 March 1998

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-kappa B 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.

* Corresponding author. Mailing address: Program in Molecular Medicine, University of Massachusetts Medical Center, 373 Plantation St., Worcester, MA 01605. Phone: (508) 856-5136. Fax: (508) 856-3210. E-mail: Tony.Ip{at}ummed.edu.

Mol Cell Biol, June 1998, p. 3527-3539, Vol. 18, No. 6
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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