MOLECULAR-CLONING OF A NOVEL TYPE-I RECEPTOR SERINE THREONINE KINASE FOR THE TGF-BETA SUPERFAMILY FROM RAT-BRAIN/

Growth factors belonging to the TGF beta superfamily bind to and signa l through a receptor complex comprising two transmembrane serine/threo nine kinases, called type and type II. Each receptor is responsible fo r the signaling of the individual TGF beta superfamily members. So far , five type II and six type I receptors have been cloned from mammalia n sources. We report here the molecular cloning of a novel type I rece ptor serine/threonine kinase, ALK7 (activin receptor-like kinase 7), f rom rat brain. ALK7 shows a significant sequence similarity with TGF b eta RI and ActRIB in the intracellular kinase domain and is quite dist inct from other type I receptors in the extracellular domain. ALK7 mRN A is expressed in embryonic and in adult rat brain, where it was local ized in superficial layers of the forebrain, the CA3 pyramidal subfiel d of hippocampus, the basal ganglia, the thalamus, and the cerebellar cortex. The functionality of the receptor was demonstrated by the iden tification of a constitutively active point mutant of ALK7 that activa tes the TGF beta/activin-responsive reporter without any ligand stimul ation. Although the endogenous ligand for ALK7 has yet to be identifie d, its extensive anatomic distribution in brain, gut, spleen, and lung suggests important roles for this orphan receptor.