Molecular cloning of a novel type I receptor serine/threonine kinase for the TGFβ superfamily from rat brain

Growth factors belonging to the TGFβ superfamily bind to and signal through a receptor complex comprising two transmembrane serine/threonine kinases, called type I and type II. Each receptor is responsible for the signaling of the individual TGFβ superfamily members. So far, five type II and six type I receptors have been cloned from mammalian sources. We report here the molecular cloning of a novel type I receptor serine/threonine kinase, ALK7 (activin receptor-like kinase 7), from rat brain. ALK7 shows a significant sequence similarity with TGFβRI and ActRIB in the intracellular kinase domain and is quite distinct from other type I receptors in the extracellular domain. ALK7 mRNA is expressed in embryonic and in adult rat brain, where it was localized in superficial layers of the forebrain, the CA3 pyramidal subfield of hippocampus, the basal ganglia, the thalamus, and the cerebellar cortex. The functionality of the receptor was demonstrated by the identification of a constitutively active point mutant of ALK7 that activates the TGFβ/activin-responsive reporter without any ligand stimulation. Although the endogenous ligand for ALK7 has yet to be identified, its extensive anatomic distribution in brain, gut, spleen, and lung suggests important roles for this orphan receptor.