Wnt family proteins are secreted and associated with the cell surface

BD Smolich, JA McMahon, AP McMahon and J Papkoff

SUGEN, Redwood City, California 94063.

Members of the Wnt gene family are proposed to function in both normal development and differentiation as well as in mammary tumorigenesis. To understand the function of Wnt proteins in these two processes, we present here a biochemical characterization of seven Wnt family members. For these studies, AtT-20 cells, a neuroendocrine cell line previously shown to efficiently process and secrete Wnt-1, was transfected with expression vectors encoding Wnt family members. All of the newly characterized Wnt proteins are glycosylated, secreted proteins that are tightly associated with the cell surface or extracellular matrix. We have also identified native Wnt proteins in retinoic acid-treated P19 embryonal carcinoma cells, and they exhibit the same biochemical characteristics as the recombinant proteins. These data suggest that Wnt family members function in cell to cell signaling in a fashion similar to Wnt-1.

Volume 4, Issue 12, pp. 1267-1275, 12/01/1993
Copyright © 1993 by The American Society for Cell Biology

This article has been cited by other articles:

				K. M. Cadigan and M. Peifer Wnt Signaling from Development to Disease: Insights from Model Systems Cold Spring Harb Perspect Biol, August 1, 2009; 1(2): a002881 - a002881. [Abstract] [Full Text] [PDF]

				M. A. Christman II, D. J. Goetz, E. Dickerson, K. D. McCall, C. J. Lewis, F. Benencia, M. J. Silver, L. D. Kohn, and R. Malgor Wnt5a is expressed in murine and human atherosclerotic lesions Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2864 - H2870. [Abstract] [Full Text] [PDF]

				L. M. Galli, T. L. Barnes, S. S. Secrest, T. Kadowaki, and L. W. Burrus Porcupine-mediated lipid-modification regulates the activity and distribution of Wnt proteins in the chick neural tube Development, September 15, 2007; 134(18): 3339 - 3348. [Abstract] [Full Text] [PDF]

				H. Komekado, H. Yamamoto, T. Chiba, and A. Kikuchi Glycosylation and palmitoylation of Wnt-3a are coupled to produce an active form of Wnt-3a Genes Cells, April 1, 2007; 12(4): 521 - 534. [Abstract] [Full Text] [PDF]

				A. Kikuchi and H. Yamamoto Regulation of Wnt Signalling by Receptor-mediated Endocytosis J. Biochem., April 1, 2007; 141(4): 443 - 451. [Abstract] [Full Text] [PDF]

				I. T. Struewing, A. Toborek, and C. D. Mao Mitochondrial and Nuclear Forms of Wnt13 Are Generated via Alternative Promoters, Alternative RNA Splicing, and Alternative Translation Start Sites J. Biol. Chem., March 17, 2006; 281(11): 7282 - 7293. [Abstract] [Full Text] [PDF]

				C. Guder, S. Pinho, T. G. Nacak, H. A. Schmidt, B. Hobmayer, C. Niehrs, and T. W. Holstein An ancient Wnt-Dickkopf antagonism in Hydra Development, March 1, 2006; 133(5): 901 - 911. [Abstract] [Full Text] [PDF]

				P. Maye, J. Zheng, L. Li, and D. Wu Multiple Mechanisms for Wnt11-mediated Repression of the Canonical Wnt Signaling Pathway J. Biol. Chem., June 4, 2004; 279(23): 24659 - 24665. [Abstract] [Full Text] [PDF]

				S. S. Huang, F.-M. Tang, Y.-H. Huang, I-H. Liu, S.-C. Hsu, S.-T. Chen, and J. S. Huang Cloning, Expression, Characterization, and Role in Autocrine Cell Growth of Cell Surface Retention Sequence Binding Protein-1 J. Biol. Chem., October 31, 2003; 278(44): 43855 - 43869. [Abstract] [Full Text] [PDF]

				M. E. van Gijn, M. J.A.P. Daemen, J. F.M. Smits, and W.M. Blankesteijn The wnt-frizzled cascade in cardiovascular disease Cardiovasc Res, July 1, 2002; 55(1): 16 - 24. [Full Text] [PDF]

				K. Tanaka, Y. Kitagawa, and T. Kadowaki Drosophila Segment Polarity Gene Product Porcupine Stimulates the Posttranslational N-Glycosylation of Wingless in the Endoplasmic Reticulum J. Biol. Chem., April 5, 2002; 277(15): 12816 - 12823. [Abstract] [Full Text] [PDF]

				L. Lo Muzio A Possible Role for the Wnt~1 Pathway in Oral Carcinogenesis Critical Reviews in Oral Biology & Medicine, January 1, 2001; 12(2): 152 - 165. [Abstract] [Full Text] [PDF]

				S Dennis, M Aikawa, W Szeto, P. d'Amore, and J Papkoff A secreted frizzled related protein, FrzA, selectively associates with Wnt-1 protein and regulates wnt-1 signaling J. Cell Sci., January 11, 1999; 112(21): 3815 - 3820. [Abstract] [PDF]

				J. Grima, C. C. S. Wong, L.-j. Zhu, S.-d. Zong, and C. Y. Cheng Testin Secreted by Sertoli Cells Is Associated with the Cell Surface, and Its Expression Correlates with the Disruption of Sertoli-Germ Cell Junctions but Not the Inter-Sertoli Tight Junction J. Biol. Chem., August 14, 1998; 273(33): 21040 - 21053. [Abstract] [Full Text] [PDF]

				S Tajbakhsh, U Borello, E Vivarelli, R Kelly, J Papkoff, D Duprez, M Buckingham, and G Cossu Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5 Development, January 11, 1998; 125(21): 4155 - 4162. [Abstract] [PDF]

				J. Grima, L.-j. Zhu, and C. Y. Cheng Testin Is Tightly Associated with Testicular Cell Membrane upon Its Secretion by Sertoli Cells whose Steady-state mRNA Level in the Testis Correlates with the Turnover and Integrity of Inter-testicular Cell Junctions J. Biol. Chem., March 7, 1997; 272(10): 6499 - 6509. [Abstract] [Full Text] [PDF]

				C. Eisenberg, R. Gourdie, and L. Eisenberg Wnt-11 is expressed in early avian mesoderm and required for the differentiation of the quail mesoderm cell line QCE-6 Development, January 1, 1997; 124(2): 525 - 536. [Abstract] [PDF]

				C. Boensch, M.-D. Kuo, D. T. Connolly, S. S. Huang, and J. S. Huang Identification, Purification, and Characterization of Cell-surface Retention Sequence-binding Proteins from Human SK-Hep Cells and Bovine Liver Plasma Membranes J. Biol. Chem., January 27, 1995; 270(4): 1807 - 1816. [Abstract] [Full Text] [PDF]