Inhibitors of protein kinases affecting cAMP-dependent proteolysis of GATA-6

摘要

We screened 95 kinase inhibitors whether they affect cAMP-dependent proteolysis of GATA-6 or not. Among them 7 inhibitors inhibited the proteolysis at the concentration range of μM around their IC50. They are inhibitors for protein kinase A (H-89 and 4- cyano-3-methylisoquinoline), c-Jun N-terminal kinase (SP600125), phosphatidylinositol 3-kinase (Wort- mannin and LY-294002), casein kinase II (TBB) and cyclin dependent kinase (Cdk1/2 inhibitor III). It is of interest how these kinases play roles in the degradation process of GATA-6 since this transcription factor is essential for development and tissue-specific gene expression of mammals. Inhibitors identified in this study would be helpful to study molecular mechanisms of phenomena in which GATA-6 participates.