The catalytic activity of the ErbB-2 receptor tyrosine kinase is essential for embryonic development.
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.
Chan
Richard
R
Department of Biology, McMaster University, Hamilton, Ontario, Canada L8S 4K1.
Hardy
William R
WR
Laing
Michael A
MA
Hardy
Sarah E
SE
Muller
William J
WJ
D000818:Animals; D002384:Catalysis; D005314:Embryonic and Fetal Development; D005728:Ganglia, Sympathetic / Q000002:abnormalities / Q000196:embryology*; D018734:Genes, erbB-2; D006321:Heart / Q000196:embryology*; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
D018719:Erb-b2 Receptor Tyrosine Kinases