Activin isoforms and other members of the TGF-beta  superfamily exert their biological effects by binding to heteromeric complexes of a type I and a type II serine-threonine kinase receptor, both of which are essential for signal transduction. Seven type I and five type II receptors, including the two type I and the two type II activin receptors, designated ActR-I(A), ActR-IB, ActR-II(A) and ActR-IIB, have been cloned from mammals. Through alternative mRNA splicing, multiple ActR-IIB isoforms can also be generated, adding to the complexity of the activin receptor system. Different activin isoforms bind with different high-affinities to the various type II isoforms. Type I activin receptors do not bind directly to activin, but will associate with the type II receptor-activin complex and initiate signal transduction. Besides the activin isoforms, ActR-II will also bind inhibin, BMP-2 and BMP-7 with lower affinities. ActR-I can also bind and form signaling complexes with the BMP-2/7-bound BMPR-II. Activin type II receptors are highly conserved. Human, mouse and rat type II activin receptors share greater than 98% amino acid sequence homology. Recombinant soluble activin type II receptors bind activin with high affinity, and are potent activin antagonists.