Activin receptors: cellular signalling by receptor serine kinases

Activins are dimeric growth and differentiation factors which signal through a heteromeric complex of receptor serine kinases. Affinity labelling of activin-responsive cells with 125I-labelled activin A reveals activin-binding species of approximately 50 and 75 kDa, known as the type I and type II receptors, respectively. Molecular cloning has yielded genes encoding two type II receptors (ActRII and ActRIIB) and at least two type I receptors (ALK2 and ALK4). These receptors are members of a larger family of receptor serine kinases, which includes receptors for transforming growth factor beta (TGF beta), bone morphogenetic proteins and the Drosophila protein, decapentaplegic. Receptors I and II form a stable complex after ligand binding, resulting in phosphorylation of receptor I by receptor II. We have begun to identify intracellular targets of these molecules by using the intracellular domains of both ActRIs and ActRIIs as probes in the two-hybrid system, a cloning strategy designed to detect interacting proteins in yeast.