Identification of a Binding Site on the Type II Activin Receptor for Activin and Inhibin

摘要: Type II activin receptors (ActRII and ActRIIB) are single-transmembrane domain serine/threonine kinase that bind to initiate the signaling cellular responses triggered by this hormone. Inhibin also binds type antagonizes many effects. Here we describe alanine scanning mutagenesis of ActRII extracellular domain. We identify a cluster three hydrophobic residues (Phe42, Trp60, Phe83) that, when individually mutated in context full-length receptor, cause disruption inhibin binding ActRII. Each alanine-substituted mutants retaining maintains ability form cross-linked complexes with supports cross-linking I receptor ALK4. Unlike wild-type ActRII, unable do not an increase transiently expressed corticotroph cell line. Together, our results implicate these forming critical surface on required for functional interactions both inhibin. This first identification transforming growth factor-β family member site may provide general basis characterizing sites other members superfamily.