Betaglycan binds inhibin and can mediate functional antagonism of activin signalling

摘要: Activins and inhibins, structurally related members of the TGF-beta superfamily growth differentiation factors, are mutually antagonistic regulators reproductive other functions. bind specific type II receptor serine kinases (ActRII or IIB) to promote recruitment phosphorylation I kinase, ALK4 (refs 7-9), which then regulates gene expression by activating Smad proteins. Inhibins also activin receptors but do not recruit ALK4, providing a competitive model for antagonism inhibin. fail antagonize in some tissues cells, however, suggesting that additional components required inhibin action. Here we show III receptor, betaglycan, can function as an co-receptor with ActRII. Betaglycan binds high affinity enhances binding cells co-expressing ActRII betaglycan. Inhibin forms crosslinked complexes both recombinant endogenously expressed betaglycan Finally, confers sensitivity cell lines otherwise respond poorly this hormone. The ability facilitate provides variation on emerging roles proteoglycans co-receptors modulating ligand-receptor sensitivity, selectivity function.