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.