Activins and Inhibins and Their Signaling

Authors

  • WYLIE VALE PHD,

    Corresponding author
    1. Clayton Foundation Laboratories for Peptide Biology and Structural Biology Laboratory, Salk Institute for Biological Studies, San Diego, California 92037, USA
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  • EZRA WIATER PHD,

    1. Clayton Foundation Laboratories for Peptide Biology and Structural Biology Laboratory, Salk Institute for Biological Studies, San Diego, California 92037, USA
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  • PETER GRAY PHD,

    1. Clayton Foundation Laboratories for Peptide Biology and Structural Biology Laboratory, Salk Institute for Biological Studies, San Diego, California 92037, USA
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  • CRAIG HARRISON PHD,

    1. Clayton Foundation Laboratories for Peptide Biology and Structural Biology Laboratory, Salk Institute for Biological Studies, San Diego, California 92037, USA
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  • LOUISE BILEZIKJIAN PHD,

    1. Clayton Foundation Laboratories for Peptide Biology and Structural Biology Laboratory, Salk Institute for Biological Studies, San Diego, California 92037, USA
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  • SENYON CHOE PHD

    1. Clayton Foundation Laboratories for Peptide Biology and Structural Biology Laboratory, Salk Institute for Biological Studies, San Diego, California 92037, USA
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Address for correspondence: Wylie Vale, PhD, Helen McLoraine Professor and Head, Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, California 92037. Voice: 858–453–4100 X1307. vale@salk.edu

Abstract

Abstract: 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-β (TGFβ) 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.

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