Protein kinase C and chemical-induced abnormal palate development

Abstract

The protein kinase C (PKC) family of proteins mediates the action of growth factors and other ligands by activating a network of transcription factors that bind to TRE sequences in the promoters of many genes that regulate cell proliferation, differentiation, extracellular matrix synthesis, apoptosis and others in a cell type-, isozymeand context-specific manner. The critical role of PKC in embryonic development is indicated by early death of embryos in which one or more of these isozymes are inactivated. Our studies together with others show that palatal PKC signalling is functional and may be essential for normal palate development. Although single gene knockouts have failed to exhibit the cleft palate (CP) phenotype, owing to compensation by other kinases, many chemicals including the mycotoxin, secalonic acid D, disrupt palatal PKC signalling leading to altered palatal mesenchymal gene expression. The potential relevance of such effects to chemical-induced CP is discussed.