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Originally published In Press as doi:10.1074/jbc.M201378200 on April 30, 2002

J. Biol. Chem., Vol. 277, Issue 28, 25697-25702, July 12, 2002
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Expression of the Human Poliovirus Receptor/CD155 Gene Is Activated by Sonic Hedgehog*

David J. SoleckiDagger §, Matthias GromeierDagger , Steffen MuellerDagger ||, Günter Bernhardt**Dagger Dagger , and Eckard WimmerDagger

From the Dagger  Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook, Stony Brook, New York 11794 and ** Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, 13092 Berlin, Germany

The human poliovirus receptor/CD155 is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. The ectodomain of CD155 mediates cell attachment to the extracellular matrix molecule vitronectin, while its intracellular domain interacts with the dynein light chain Tctex-1. CD155 is a primate-restricted gene that is expressed during development in mesenchymal tissues and ventrally derived structures within the CNS. Its function in adults is as yet unknown, but significantly, CD155 is aberrantly expressed in neuroectodermal tumors. We show that the expression of CD155 mRNA is up-regulated when human Ntera2 cells are treated with purified Sonic hedgehog (Shh) protein. Reporter gene expression driven by the CD155 core promoter is activated by Shh in transient co-transfection assays. Analysis of the CD155 core promoter indicates that an intact GLI binding site is required for Shh activation. In addition, overexpression of Gli1 or Gli3 potently activates reporter gene expression driven by the CD155 core promoter. These data identify the CD155 gene as a transcriptional target of Shh, a finding that has significance for the normal function of CD155 during development and the expression of CD155 in neuroectodermal tumors.

* This work was supported in part by National Institutes of Health Grant AI39485 (to E. W.).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.

§ A member of the graduate program in Molecular and Cellular Biology, State University of New York at Stony Brook and recipient of a grant from the Deutscher Akademischer Austauschdienst (DAAD). To whom inquiries should be addressed: Laboratory of Developmental Neurobiology, The Rockefeller University, 1230 York Ave., New York, NY 10021. E-mail: soleckd@mail.rockefeller.edu.

Recipient of a Burroughs Wellcome Career Award. Current address: Dept. of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710.

|| Supported by a doctoral fellowship of BoehringerIngelheim Fonds, Heidesheim, Germany.

Dagger Dagger Supported by Grant BE1886/1-2 from the Deutsche Forschungsgemeinschaft.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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