Activin B can signal through both ALK4 and ALK7 in gonadotrope cells

Abstract

Background: Activins stimulate pituitary FSH synthesis via transcriptional regulation of the FSHbeta subunit gene (Fshb). Like other members of the TGFbeta superfamily, these ligands signal through complexes of type I and type II receptor serine/threonine kinases. The type I receptors, or activin receptor-like kinases (ALKs), propagate intracellular signals upon ligand binding and phosphorylation by associated type II receptors. ALK4 is generally regarded as the type I receptor for activins; however, recent data suggested that activin B and AB might also signal through ALK7. Here, we examined a role for ALK7 in activin B-regulated Fshb transcription.

Activin A, B and AB decrease progesterone production by down-regulating StAR in human granulosa cells

“…Unfortunately, mice depleted of ALK4 are embryonic lethal, which prevented us from directly assessing their reproductive phenotypes (Gu et al, 1998). Outside the reproductive system, aside from ALK4, activin B or activin AB has been reported to signal and act through ALK7 in murine gonadotrope LβT2 and murine pancreatic cells (Bernard et al, 2006;Tsuchida et al, 2004). These discrepancies may be attributed to interspecies differences or the mechanisms in which activin-driven regulation of cellular functions are cell type-or tissue type-dependent.…”

Seminal fluid factors regulate activin A and follistatin synthesis in female cervical epithelial cells

“…70 INHBA signals via the classical TGFB (SMAD2/3) signalling pathway, however unlike TGFB, it binds to distinct type II (ActIIRA and ActIIRB) and type I (ALK2, ALK4 and ALK7) receptors [26][27][28]. INHBA bioavailability is controlled by the binding protein and signalling inhibitor follistatin (FST), which completely prevents INHBA from binding to the type II receptor [29][30][31].…”

Cycloheximide inhibits follicle-stimulating hormone β subunit transcription by blocking de novo synthesis of the labile activin type II receptor in gonadotrope cells

“…Some activin isoforms can also signal via a second type I receptor, ALK7 [8,9]. Activins bind initially to type II receptors, which then trans-phosphorylate and activate type I receptors.…”