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

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2002, p. 1073-1078, Vol. 22, No. 4
0270-7306/01/$04.00+0     DOI: 10.1128/MCB.22.4.1073-1078.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Catalytic Activity of the ErbB-2 Receptor Tyrosine Kinase Is Essential for Embryonic Development

Departments of Biology,¹ Biochemistry,² Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada L8S 4K1³

Received 17 September 2001/ Returned for modification 25 October 2001/ Accepted 2 November 2001

Activation of the epidermal growth factor receptor (EGFR) family is thought to play a critical role in both embryogenesis and oncogenesis. The diverse biological activities of the EGFR family are achieved through various ligand-receptor and receptor-receptor interactions. One receptor that has been found to play a central role in this signaling network is ErbB-2/Neu, and it is considered the preferred heterodimerization partner for other members of the EGFR family. To assess the importance of the catalytic activity of ErbB-2 in embryonic development, we have generated mice expressing a kinase-dead erbB-2 cDNA under the transcriptional control of the endogenous promoter. Here, we show that mice homozygous for the kinase-dead erbB-2 allele die at midgestation and display the same spectrum of embryonic defects seen in erbB-2 knockout mutants. These observations suggest that the catalytic activity of ErbB-2 is essential for normal embryonic development.

This article has been cited by other articles:

• Fan, Y.-X., Wong, L., Ding, J., Spiridonov, N. A., Johnson, R. C., Johnson, G. R. (2008). Mutational Activation of ErbB2 Reveals a New Protein Kinase Autoinhibition Mechanism. J. Biol. Chem. 283: 1588-1596 [Abstract] [Full Text]  
• Nethery, D. E., Moore, B. B., Minowada, G., Carroll, J., Faress, J. A., Kern, J. A. (2005). Expression of mutant human epidermal receptor 3 attenuates lung fibrosis and improves survival in mice. J. Appl. Physiol. 99: 298-307 [Abstract] [Full Text]  
• Khoury, H., Naujokas, M. A., Zuo, D., Sangwan, V., Frigault, M. M., Petkiewicz, S., Dankort, D. L., Muller, W. J., Park, M. (2005). HGF Converts ErbB2/Neu Epithelial Morphogenesis to Cell Invasion. Mol. Biol. Cell 16: 550-561 [Abstract] [Full Text]  
• Chan, R., Hardy, W. R., Dankort, D., Laing, M. A., Muller, W. J. (2004). Modulation of Erbb2 signaling during development: a threshold level of Erbb2 signaling is required for development. Development 131: 5551-5560 [Abstract] [Full Text]  
• Andrechek, E. R., Hardy, W. R., Laing, M. A., Muller, W. J. (2004). Germ-line expression of an oncogenic erbB2 allele confers resistance to erbB2-induced mammary tumorigenesis. Proc. Natl. Acad. Sci. USA 101: 4984-4989 [Abstract] [Full Text]  
• Leone, F., Perissinotto, E., Cavalloni, G., Fonsato, V., Bruno, S., Surrenti, N., Hong, D., Capaldi, A., Geuna, M., Piacibello, W., Aglietta, M. (2003). Expression of the c-ErbB-2/HER2 proto-oncogene in normal hematopoietic cells. J. Leukoc. Biol. 74: 593-601 [Abstract] [Full Text]  
• Andrechek, E. R., Hardy, W. R., Girgis-Gabardo, A. A., Perry, R. L. S., Butler, R., Graham, F. L., Kahn, R. C., Rudnicki, M. A., Muller, W. J. (2002). ErbB2 Is Required for Muscle Spindle and Myoblast Cell Survival. Mol. Cell. Biol. 22: 4714-4722 [Abstract] [Full Text]