Activins and inhibins and their signaling.
Activins and inhibins, which were discovered by virtue of their abilities to stimulate or inhibit, respectively, the secretion of FSH, are members of the transforming growth factor-beta (TGFbeta) superfamily and exert a broad range of effects on the diffentiation, proliferation and functions of numerous cell types. Activins interact with two structurally related classes of serine/threonine kinase receptors (type I and type II). Inhibin antagonizes activin by binding to the proteoglycan, betaglycan, and forming a stable complex with and, thereby, sequestering type II activin receptors while excluding type I receptors. If betaglycan is present, inhibin can also antagonize those bone morphogenic proteins (BMPs) whose signaling is dependent upon access to type II activin receptors. Recent insights regarding the structures of ligands, receptors and their signaling complexes are providing the basis for the development of therapeutics capable of modulating fertility and numerous pathophysiologic processes.
Vale
Wylie
W
Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, San Diego, California 92037, USA. vale@salk.edu
Wiater
Ezra
E
Gray
Peter
P
Harrison
Craig
C
Bilezikjian
Louise
L
Choe
Senyon
S
D030201:Activin Receptors, Type I / Q000378:metabolism; D030301:Activin Receptors, Type II / Q000378:metabolism; D028341:Activins / Q000378:metabolism*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007265:Inhibins / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D019485:Bone Morphogenetic Proteins; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D028341:Activins; C071736:betaglycan; D007265:Inhibins; D005640:Follicle Stimulating Hormone; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II