The biological responses of the transforming growth factor beta (TGF-beta)
superfamily are induced by activation of a receptor complex and Smad protei
ns. 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 MING cells. The constitutively
active form of ALK7, ALK7(T194D), activated Smad3 and a chimeric Smad prote
in, 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 resul
ts indicate that the ALK7 signal regulates nuclear localization and activat
ion of Smad2 and Smad3, and the MH1 domain of Smad2 has inhibitory effects
on the nuclear localization. (C) 1999 Academic Press.