Serpin-1 splicing isoform J inhibits the proSpatzle-activating proteinase HP8 to regulate expression of antimicrobial hemolymph proteins in Manduca sexta

被引：55

作者：

An, Chunju ^{[1
]}

Ragan, Emily J. ^{[1
]}

Kanost, Michael R. ^{[1
]}

机构：

[1] Kansas State Univ, Dept Biochem, Manhattan, KS 66506 USA

来源：

DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY | 2011年 / 35卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Serpin; Clip domain serine proteinase; Toll signaling pathway; Hemolymph; Immunity; MOSQUITO AEDES-AEGYPTI; TOLL PATHWAY; PROTEOLYTIC ACTIVATION; IMMUNE-RESPONSE; DROSOPHILA; INSECTS; FAMILY; PEPTIDOGLYCAN; MELANIZATION; SUPERFAMILY;

D O I：

10.1016/j.dci.2010.09.004

中图分类号：

S9 [水产、渔业];

学科分类号：

0908 ;

摘要：

The innate immune system of insects include the Toll pathway, which is mediated by an extracellular serine proteinase cascade. In the tobacco hornworm, Manduca sexta, hemolymph proteinase 8 (HP8) promotes the synthesis of antimicrobial proteins by cleaving proSpatzle, the putative ligand of M. sexta Toll. HP8 has been observed to form a complex in hemolymph with M. sexta serpin-1, which has multiple alternative splicing isoforms. To investigate the regulation of HP8 and its processing of proSpatzle, we characterized the interaction of recombinant HP8 with serpin-1 isoform J (serpin-1J). Recombinant serpin-1J formed an SOS-stable complex with HP8 in vitro. The association rate constant of serpin-1J and HP8 was 1.3 x 10(4) M(-1)s(-1), with a stoichiometry of inhibition of 5.4. Serpin-1J inhibited the cleavage of proSpatzle by HP8. Injection of serpin-1J into M. sexta larvae resulted in decreased bacteria-induced antimicrobial activity in hemolymph and reduced expression of cecropin, attacin and hemolin mRNA in fat body. Altogether, these results suggest that serpin-1J functions to inhibit HP8 and thereby modulates the concentration of active Spatzle to regulate the. Toll pathway response in M. sexta. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：135 / 141

页数：7

共 41 条

[11] Serpin structure, mechanism, and function [J].

Gettins, PGW .

CHEMICAL REVIEWS, 2002, 102 (12) :4751-4803

[12]

GUBB D, 2007, MOL CELLULAR ASPECTS, P207

[13] Differential expansion and evolution of the exon family encoding the Serpin-1 reactive centre loop has resulted in divergent serpin repertoires among the Lepidoptera [J].

Hegedus, Dwayne D. ;

Erlandson, Martin ;

Baldwin, Douglas ;

Hou, Xingwei ;

Chamankhah, Mahmood .

GENE, 2008, 418 (1-2) :15-21

[14] Phylogeny of the serpin superfamily: Implications of patterns of amino acid conservation for structure and function [J].

Irving, JA ;

Pike, RN ;

Lesk, AM ;

Whisstock, JC .

GENOME RESEARCH, 2000, 10 (12) :1845-1864

[15] Prophenoloxidase-activating proteinase-3 (PAP-3) from Manduca sexta hemolymph:: a clip-domain serine proteinase regulated by serpin-1J and serine proteinase homologs [J].

Jiang, HB ;

Wang, Y ;

Yu, XQ ;

Zhu, YF ;

Kanost, M .

INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2003, 33 (10) :1049-1060

[16] Organization of serpin gene-1 from Manduca sexta - Evolution of a family of alternate exons encoding the reactive site loop [J].

Jiang, HB ;

Wang, Y ;

Huang, YL ;

Mulnix, AB ;

Kadel, J ;

Cole, K ;

Kanost, MR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (45) :28017-28023

[17] The clip-domain family of serine proteinases in arthropods [J].

Jiang, HB ;

Kanost, MR .

INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2000, 30 (02) :95-105

[18] Characterization and functional analysis of 12 naturally occurring reactive site variants of serpin-1 from Manduca sexta [J].

Jiang, HB ;

Kanost, MR .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (02) :1082-1087

[19] Three Pairs of Protease-Serpin Complexes Cooperatively Regulate the Insect Innate Immune Responses [J].

Jiang, Rui ;

Kim, Eun-Hye ;

Gong, Ji-Hee ;

Kwon, Hyun-Mi ;

Kim, Chan-Hee ;

Ryu, Kyoung-Hwa ;

Park, Ji-Won ;

Kurokawa, Kenji ;

Zhang, Jinghai ;

Gubb, David ;

Lee, Bok-Luel .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (51) :35652-35658

[20] Serine proteinase inhibitors in arthropod immunity [J].

Kanost, MR .

DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY, 1999, 23 (4-5) :291-301

← 1 2 3 4 5 →