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  • Original Paper
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Chimeric Wnt proteins define the amino-terminus of Wnt-1 as a transformation-specific determinant

Oncogene volume 18, pages 149–156 (1999)Cite this article

Abstract

Wnt-1 induces morphological transformation of C57MG mammary epithelial cells and accumulation of cytosolic β-catenin whereas Wnt-5a has no effect. To identify regions within the 370 amino acid Wnt-1 protein required for these functions we tested eleven chimeric genes that contained variable amounts of Wnt-1 and Wnt-5a sequence. Transformation and β-catenin regulation in C57MG cells is controlled by amino acids that lie within 186 residues of the amino terminus of Wnt-1. Small substitutions between residues 186 and 292 reduced Wnt-1 activity. Replacement of the carboxy terminal 79 amino acids of Wnt-1 by Wnt-5a did not affect function. These results were supported by transient expression asssays in 293 cells wherein β-catenin accumulated in the cytoplasm in response to ectopic Wnt-1 expression. In 293 cells, a larger region of the amino-terminus of Wnt-1 was found to be required for β-catenin regulation. Nonfunctional chimeras that contained at least 99 amino terminal Wnt-1 residues inhibited Wnt-1 stimulation of 293 cells. One of these chimeras inhibited both Wnt-1 and Wnt-3 activity suggesting that Wnt-1 and Wnt-3 interact with a common signaling component.

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Acknowledgements

The authors wish to thank Rita Yeretsian for technical support; Eve Vagg and Rachel Yarmolinsky for graphics arts assistance; Drs Marielba Zerlin and James Goldman for their assistance and making available their photomicrography equipment and Drs David Cobrinik, John Krolewski and Hendrik Uyttendaele for providing comments on the manuscript. This work was supported by an American Cancer Society Grant DB-81, a US Army Medical Research and Material Command Grant DAMD17-94-J-4069, and the Marilyn Bokemeier Sperry Fund (to JK). SDR was supported by a Student Undergraduate Research Fellowship from Columbia University.

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  1. Department of Pathology and Center for Reproductive Sciences, Columbia University, College of Physicians and Surgeons, 630 W. 168th Street, New York, 10032, New York, USA

    Martin A Julius, Seema D Rai & Jan Kitajewski

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  1. Martin A Julius
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  2. Seema D Rai
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  3. Jan Kitajewski
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Julius, M., Rai, S. & Kitajewski, J. Chimeric Wnt proteins define the amino-terminus of Wnt-1 as a transformation-specific determinant. Oncogene 18, 149–156 (1999). https://doi.org/10.1038/sj.onc.1202268

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