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Originally published In Press as doi:10.1074/jbc.M305986200 on July 18, 2003

J. Biol. Chem., Vol. 278, Issue 40, 38579-38585, October 3, 2003
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Insect Cytokine Growth-blocking Peptide Triggers a Termination System of Cellular Immunity by Inducing Its Binding Protein*

Yasuko Matsumoto, Yasunori Oda, Masahide Uryu and Yoichi Hayakawa {ddagger}

From the Institute of Low Temperature Science, Hokkaido University, Sapporo 060-0819, Japan

Growth-blocking peptide (GBP) is a 25-amino acid cytokine found in lepidopteran insects that possesses diverse biological activities such as stimulation of immune cells (plasmatocytes), cell proliferation, and larval growth regulation. We found another novel function of GBP that induces a hemolysis of another class of blood cells (oenocytoids). In the lysate of oenocytoids we identified a GBP-binding protein that shows a specific affinity for GBP. The characterization of purified GBP-binding protein and its cDNA demonstrated it as a 49.5-kDa novel protein with a C-terminal region displaying limited homology to several insect lipoproteins. Results of Northern and Western blotting indicated that the GBP-binding protein should be synthesized only in blood cells. Immunoelectron microscopic analyses confirmed that indirect immunoreactive signals were mostly localized in oenocytoids. Kinetic and biological analyses of interaction between GBP and the binding protein showed their strong binding was followed by clearance of GBP from hemolymph, thus indicating that this protein might function as an inhibitory factor against GBP. Based on these results, we propose that insect cytokine GBP shows multifunctions even in cellular immunity: it serves to stimulate immune cells and afterward silences its own action by inducing the binding protein through specific hemolysis.


Received for publication, June 6, 2003 , and in revised form, July 15, 2003.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AB098260.

* This work was supported by the Program for Promotion of Basic Research Activities for Innovative Bioscience. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} To whom correspondence should be addressed. Tel.: 011-706-6880; Fax: 011-706-7142; E-mail: hayakawa{at}lowtem.hokudai.ac.jp.


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