Molecular cloning of activin type I and type II receptors and differential regulation of their expression by activin in grass carp pituitary cells.

Activins, like other members of the transforming growth factor-beta superfamily, signal via two structurally related transmembrane serine/threonine kinase receptors classified as types II and I. Two cDNAs encoding activin type IIB receptor (ActRIIB) and activin type IB receptor (ActRIB) were cloned and characterized from grass carp. The deduced ActRIIB protein of 510 amino acids shared 79-90% identity with those in other vertebrates, while the predicted ActRIB protein of 505 amino acids exhibited high sequence identity (80-96%) to its counterparts in human, rat, mouse, frog, and zebrafish. Comparative analysis showed that both receptors contained the conserved amino acid residues required for ligand binding, and comprised the characteristic regions of an extracellular ligand binding domain, a single transmembrane region, and an intracellular serine/threonine kinase domain. Real-time PCR analysis revealed that both ActRIIB and ActRIB transcripts were ubiquitously expressed in all tissues examined, in particular with high expression levels in extra-gonadal tissues, including pituitary, brain, and liver. Using a static incubation approach, the feedback effects of exogenous activin on ActRIIB and ActRIB mRNA expression were examined at the pituitary level. Activin significantly stimulated ActRIB mRNA expression in a time- and dose-dependent manner, but had no effect on ActRIIB mRNA levels. These findings support the notion that activin receptors may serve as a local regulatory point involving in pituitary function of activin in fish.