This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vogel, W. F.
Right arrow Articles by Pawson, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vogel, W. F.
Right arrow Articles by Pawson, T.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2001, p. 2906-2917, Vol. 21, No. 8
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.8.2906-2917.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Discoidin Domain Receptor 1 Tyrosine Kinase Has an Essential Role in Mammary Gland Development

Wolfgang F. Vogel,1,* Attila Aszódi,2 Frauke Alves,3 and Tony Pawson1,4

Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5,1 and Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5S 1A8,4 Canada; Department of Experimental Pathology, Lund University Hospital, 22185 Lund, Sweden2; and Department of Hematology and Oncology, University of Göttingen, 37075 Göttingen, Germany3

Received 24 October 2000/Returned for modification 7 December 2000/Accepted 26 January 2001

Various types of collagen have been identified as potential ligands for the two mammalian discoidin domain receptor tyrosine kinases, DDR1 and DDR2. Here, we used a recombinant fusion protein between the extracellular domain of DDR1 and alkaline phosphatase to detect specific receptor binding sites during mouse development. Major sites of DDR1-binding activity, indicative of ligand expression, were found in skeletal bones, the skin, and the urogenital tract. Ligand expression in the uterus during implantation and in the mammary gland during pregnancy colocalized with the expression of the DDR1 receptor. The generation of DDR1-null mice by gene targeting yielded homozygous mutant animals that were viable but smaller in size than control littermates. The majority of mutant females were unable to bear offspring due to a lack of proper blastocyst implantation into the uterine wall. When implantation did occur, the mutant females were unable to lactate. Histological analysis showed that the alveolar epithelium failed to secrete milk proteins into the lumen of the mammary gland. The lactational defect appears to be caused by hyperproliferation and abnormal branching of mammary ducts. These results suggest that DDR1 is a key mediator of the stromal-epithelial interaction during ductal morphogenesis in the mammary gland.

* Corresponding author. Present address: Georg-Speyer-Haus Institute for Biomedical Research, Johann Wolfgang Goethe Universität Frankfurt, Paul-Ehrlich-Strasse 42-44, 60596 Frankfurt am Main, Germany. Phone: 49-69-63395 222. Fax: 49-69-63395 297. E-mail: W.Vogel{at}em.uni-frankfurt.de.

Molecular and Cellular Biology, April 2001, p. 2906-2917, Vol. 21, No. 8
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.8.2906-2917.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Perera, C. N., Spalding, H. S., Mohammed, S. I., Camarillo, I. G. (2008). Identification of Proteins Secreted from Leptin Stimulated MCF-7 Breast Cancer Cells: A Dual Proteomic Approach. Exp. Biol. Med. 233: 708-720 [Abstract] [Full Text]  
  • Abdulhussein, R., Koo, D. H. H., Vogel, W. F. (2008). Identification of Disulfide-linked Dimers of the Receptor Tyrosine Kinase DDR1. J. Biol. Chem. 283: 12026-12033 [Abstract] [Full Text]  
  • Konitsiotis, A. D., Raynal, N., Bihan, D., Hohenester, E., Farndale, R. W., Leitinger, B. (2008). Characterization of High Affinity Binding Motifs for the Discoidin Domain Receptor DDR2 in Collagen. J. Biol. Chem. 283: 6861-6868 [Abstract] [Full Text]  
  • Roarty, K., Serra, R. (2007). Wnt5a is required for proper mammary gland development and TGF-{beta}-mediated inhibition of ductal growth. Development 134: 3929-3939 [Abstract] [Full Text]  
  • Matsuyama, W., Mitsuyama, H., Ono, M., Shirahama, Y., Higashimoto, I., Osame, M., Arimura, K. (2007). Discoidin domain receptor 1 contributes to eosinophil survival in an NF-{kappa}B-dependent manner in Churg-Strauss syndrome. Blood 109: 22-30 [Abstract] [Full Text]  
  • Flamant, M., Placier, S., Rodenas, A., Curat, C. A., Vogel, W. F., Chatziantoniou, C., Dussaule, J.-C. (2006). Discoidin Domain Receptor 1 Null Mice Are Protected against Hypertension-Induced Renal Disease. J. Am. Soc. Nephrol. 17: 3374-3381 [Abstract] [Full Text]  
  • Das, S., Ongusaha, P. P., Yang, Y. S., Park, J.-M., Aaronson, S. A., Lee, S. W. (2006). Discoidin Domain Receptor 1 Receptor Tyrosine Kinase Induces Cyclooxygenase-2 and Promotes Chemoresistance through Nuclear Factor-{kappa}B Pathway Activation. Cancer Res. 66: 8123-8130 [Abstract] [Full Text]  
  • Avivi-Green, C., Singal, M., Vogel, W. F. (2006). Discoidin Domain Receptor 1-deficient Mice Are Resistant to Bleomycin-induced Lung Fibrosis. Am. J. Respir. Crit. Care Med. 174: 420-427 [Abstract] [Full Text]  
  • Noordeen, N. A., Carafoli, F., Hohenester, E., Horton, M. A., Leitinger, B. (2006). A Transmembrane Leucine Zipper Is Required for Activation of the Dimeric Receptor Tyrosine Kinase DDR1. J. Biol. Chem. 281: 22744-22751 [Abstract] [Full Text]  
  • Matsuyama, W., Watanabe, M., Shirahama, Y., Mitsuyama, H., Higashimoto, I., Osame, M., Arimura, K. (2006). Discoidin Domain Receptor 1 Contributes to the Survival of Lung Fibroblast in Idiopathic Pulmonary Fibrosis. Am. J. Pathol. 168: 866-877 [Abstract] [Full Text]  
  • Atabai, K., Fernandez, R., Huang, X., Ueki, I., Kline, A., Li, Y., Sadatmansoori, S., Smith-Steinhart, C., Zhu, W., Pytela, R., Werb, Z., Sheppard, D. (2005). Mfge8 Is Critical for Mammary Gland Remodeling during Involution. Mol. Biol. Cell 16: 5528-5537 [Abstract] [Full Text]  
  • Shyu, K.-G., Chao, Y.-M., Wang, B.-W., Kuan, P. (2005). Regulation of Discoidin Domain Receptor 2 by Cyclic Mechanical Stretch in Cultured Rat Vascular Smooth Muscle Cells. Hypertension 46: 614-621 [Abstract] [Full Text]  
  • Thomas, E. K., Nakamura, M., Wienke, D., Isacke, C. M., Pozzi, A., Liang, P. (2005). Endo180 Binds to the C-terminal Region of Type I Collagen. J. Biol. Chem. 280: 22596-22605 [Abstract] [Full Text]  
  • Xu, L., Peng, H., Wu, D., Hu, K., Goldring, M. B., Olsen, B. R., Li, Y. (2005). Activation of the Discoidin Domain Receptor 2 Induces Expression of Matrix Metalloproteinase 13 Associated with Osteoarthritis in Mice. J. Biol. Chem. 280: 548-555 [Abstract] [Full Text]  
  • Abdulhussein, R., McFadden, C., Fuentes-Prior, P., Vogel, W. F. (2004). Exploring the Collagen-binding Site of the DDR1 Tyrosine Kinase Receptor. J. Biol. Chem. 279: 31462-31470 [Abstract] [Full Text]  
  • Ortega-Velazquez, R., Gonzalez-Rubio, M., Ruiz-Torres, M. P., Diez-Marques, M. L., Iglesias, M. C., Rodriguez-Puyol, M., Rodriguez-Puyol, D. (2004). Collagen I upregulates extracellular matrix gene expression and secretion of TGF-{beta}1 by cultured human mesangial cells. Am. J. Physiol. Cell Physiol. 286: C1335-C1343 [Abstract] [Full Text]  
  • Ferri, N., Carragher, N. O., Raines, E. W. (2004). Role of Discoidin Domain Receptors 1 and 2 in Human Smooth Muscle Cell-Mediated Collagen Remodeling: Potential Implications in Atherosclerosis and Lymphangioleiomyomatosis. Am. J. Pathol. 164: 1575-1585 [Abstract] [Full Text]  
  • Matsuyama, W., Wang, L., Farrar, W. L., Faure, M., Yoshimura, T. (2004). Activation of Discoidin Domain Receptor 1 Isoform b with Collagen Up-Regulates Chemokine Production in Human Macrophages: Role of p38 Mitogen-Activated Protein Kinase and NF-{kappa}B. J. Immunol. 172: 2332-2340 [Abstract] [Full Text]  
  • Wienke, D., MacFadyen, J. R., Isacke, C. M. (2003). Identification and Characterization of the Endocytic Transmembrane Glycoprotein Endo180 as a Novel Collagen Receptor. Mol. Biol. Cell 14: 3592-3604 [Abstract] [Full Text]  
  • Fassett, J. T., Tobolt, D., Nelsen, C. J., Albrecht, J. H., Hansen, L. K. (2003). The Role of Collagen Structure in Mitogen Stimulation of ERK, Cyclin D1 Expression, and G1-S Progression in Rat Hepatocytes. J. Biol. Chem. 278: 31691-31700 [Abstract] [Full Text]  
  • Leitinger, B. (2003). Molecular Analysis of Collagen Binding by the Human Discoidin Domain Receptors, DDR1 and DDR2. IDENTIFICATION OF COLLAGEN BINDING SITES IN DDR2. J. Biol. Chem. 278: 16761-16769 [Abstract] [Full Text]  
  • Muschler, J., Levy, D., Boudreau, R., Henry, M., Campbell, K., Bissell, M. J. (2002). A Role for Dystroglycan in Epithelial Polarization: Loss of Function in Breast Tumor Cells. Cancer Res. 62: 7102-7109 [Abstract] [Full Text]  
  • Curat, C. A., Vogel, W. F. (2002). Discoidin Domain Receptor 1 Controls Growth and Adhesion of Mesangial Cells. J. Am. Soc. Nephrol. 13: 2648-2656 [Abstract] [Full Text]  
  • Mercurio, A. M. (2002). Lessons from the {alpha}2 Integrin Knockout Mouse. Am. J. Pathol. 161: 3-6 [Full Text]  
  • Hou, G., Vogel, W. F., Bendeck, M. P. (2002). Tyrosine Kinase Activity of Discoidin Domain Receptor 1 Is Necessary for Smooth Muscle Cell Migration and Matrix Metalloproteinase Expression. Circ. Res. 90: 1147-1149 [Abstract] [Full Text]  
  • Wiseman, B. S., Werb, Z. (2002). Stromal Effects on Mammary Gland Development and Breast Cancer. Science 296: 1046-1049 [Abstract] [Full Text]  
  • Curat, C. A., Eck, M., Dervillez, X., Vogel, W. F. (2001). Mapping of Epitopes in Discoidin Domain Receptor 1 Critical for Collagen Binding. J. Biol. Chem. 276: 45952-45958 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»