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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

Richard Chan,1 William R. Hardy,1 Michael A. Laing,1 Sarah E. Hardy,1 and William J. Muller1,2,3*

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.

* Corresponding author. Mailing address: McMaster University, Life Sciences Building 327, 1280 Main St. West, Hamilton, Ontario, Canada L8S 4K1. Phone: (905) 525-9140, ext. 27306. Fax: (905) 521-2955. E-mail: mullerw{at}mcmaster.ca.

Molecular and Cellular Biology, February 2002, p. 1073-1078, Vol. 22, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/MCB.22.4.1073-1078.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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  • 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]  
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