The biological responses of the transforming growth factor beta (TGF-beta) superfamily are induced by activation of a receptor complex and Smad proteins. We surveyed the TGF-beta superfamily receptors using the degenerate PCR strategy, and found activin receptor-like kinase 7 (ALK7) to be abundantly expressed in fetal rat pancreatic islets. ALK7 is also expressed in adult rat islets and pancreatic beta-cell-derived MIN6 cells. The constitutively active form of ALK7, ALK7(T194D), activated Smad3 and a chimeric Smad protein, Smad3-2, containing the MH1 domain of Smad3 and the MH2 domain of Smad2, and translocated them to nuclei and then induced activation of the human PAI-1 promoter. However, neither Smad2 nor Smad2-3 protein, containing the MH1 domain of Smad2 and the MH2 domain of Smad3 were activated. These results indicate that the ALK7 signal regulates nuclear localization and activation of Smad2 and Smad3, and the MH1 domain of Smad2 has inhibitory effects on the nuclear localization.
Copyright 1999 Academic Press.