Cloning of a Novel Type II Serine/Threonine Kinase Receptor through Interaction with the Type I Transforming Growth Factor-β Receptor (∗)

The transforming growth factor-β (TGF-β) superfamily comprises a number of molecules that are involved in a wide variety of biological processes. Specific receptors for several members of this family have been molecularly identified, forming a new category of transmembrane serine/threonine kinase receptors. The type I and type II receptor interact both physically and functionally, thereby cooperating to generate intracellular signals. The yeast two-hybrid system was used to identify proteins that can interact with the cytoplasmic region of the type I TGF-β receptor. One of the proteins identified encodes a novel putative serine/threonine kinase receptor. Sequence analysis suggests that this molecule belongs to the type II receptor class. This receptor, however, is distinct from other type II receptors in having an extraordinarily long C-terminal tail region. The pattern of expression in adult tissues is different from that of other known type II receptors; it is highly expressed in heart and liver. In the yeast system, the cytoplasmic regions of different combinations of type I and type II receptors heterodimerize, providing a new cloning strategy for the large number of serine/threonine kinase receptors likely to exist for the many ligands of the TGF-β superfamily.