A Single STAT Recruitment Module in a Chimeric Cytokine Receptor Complex Is Sufficient for STAT Activation

doi:10.1074/jbc.272.8.5269

A Single STAT Recruitment Module in a Chimeric Cytokine Receptor Complex Is Sufficient for STAT Activation*

From the Institute of Biochemistry, Rheinisch-Westfälische Technische Hochschule Aachen, 52057 Aachen, Germany, and
^¶ Flanders Interuniversity Institute for Biotechnology, Department of Medical Protein Chemistry, Molecular Biology Unit, University of Ghent, K. L. Ledeganckstraat 35, B-9000 Ghent, Belgium

^‡ To whom correspondence should be sent:
Inst. of Biochemistry, RWTH Aachen, Pauwelsstrasse, 52057 Aachen, Germany.
Tel.: 49-241-8088838; Fax: 49-241-8888428; E-mail: behrmann{at}rwth-aachen.de

↵^§ Present address: GSF-Neuherberg, Institute of Molecular Virology, 85764 Oberschleissheim, Germany.

Abstract

We established a system of receptor chimeras that enabled us to induce heterodimerization of different cytoplasmic tails. Fusion constructs were created that are composed of the extracellular parts of the interleukin-5 receptor α and β chains, respectively, and the transmembrane and intracellular parts of gp130, the signal transducing chain of the interleukin-6 receptor complex. In COS-7 transfectants we observed a dose-dependent interleukin-5-inducible STAT1 activation for which the presence of both the α and the β chain chimera was needed. No STAT activity was detected if one of the cytoplasmic tails of the receptor complex was deleted, indicating that STAT activity resulted from a receptor dimer rather than from higher receptor aggregates.

We further investigated whether dimerization of STAT1 depends on the juxtaposition of two STAT recruitment modules in a receptor complex. We show that a receptor dimer with only a single STAT1 docking site was still able to lead to STAT1 activation. This indicates that the formation of a paired set of STAT binding sites in a receptor complex is not the prerequisite for STAT factor dimerization. Our findings are discussed in view of alternative STAT dimerization models.

Footnotes

↵* This work has been supported by the Deutsche Forschungsgemeinschaft, Bonn, Germany and by Fonds der Chemischen Industrie, Frankfurt am Main, Germany. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

IFN

interferon

SH2

Src homology 2

IL

interleukin

EMSA

electrophoretic mobility shift assay

SIE

sis-inducible element

GM-CSF

granulocyte-macrophage colony-stimulating factor.
↵² J. Van der Heyden and J. Tavernier, unpublished results.
- Received August 13, 1996.
- Revision received November 22, 1996.