NDLI: Transforming Growth Factor-β Family Ligands Can Function as Antagonists by Competing for Type II Receptor Binding

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Transforming Growth Factor-β Family Ligands Can Function as Antagonists by Competing for Type II Receptor Binding

Content Provider	Scilit
Author	Aykul, Senem Martinez-Hackert, Erik
Copyright Year	2016
Description	Journal: Journal of Biological Chemistry Transforming growth factor-β (TGF-β) family ligands are pleiotropic cytokines. Their physiological activities are not determined by a simple coupling of stimulus and response, but depend critically on context, i.e. the interplay of receptors, ligands, and regulators that form the TGF-β signal transduction system of a cell or tissue. How these different components combine to regulate signaling activities remains poorly understood. Here, we describe a ligand-mediated mechanism of signaling regulation. Based on the observation that the type II TGF-β family receptors ActRIIA, ActRIIB, and BMPRII interact with a large group of overlapping ligands at overlapping epitopes, we hypothesized high affinity ligands compete with low affinity ligands for receptor binding and signaling. We show activin A and other high affinity ligands directly inhibited signaling by the low affinity ligands BMP-2, BMP-7, and BMP-9. We demonstrate activin A functions as a competitive inhibitor that blocks the ligand binding epitope on type II receptors. We propose binding competition and signaling antagonism are integral functions of the TGF-β signal transduction system. These functions could help explain how activin A modulates physiological signaling during extraordinary cellular responses, such as injury and wound healing, and how activin A could elicit disease phenotypes such as cancer-related muscle wasting and fibrosis.
Related Links	http://www.jbc.org/content/291/20/10792.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865925/pdf http://www.jbc.org/article/S0021925820401103/pdf
Ending Page	10804
Page Count	13
Starting Page	10792
ISSN	00219258
e-ISSN	1083351X
DOI	10.1074/jbc.m115.713487
Journal	Journal of Biological Chemistry
Issue Number	20
Volume Number	291
Language	English
Publisher	Elsevier BV
Publisher Date	2016-05-01
Access Restriction	Open
Subject Keyword	Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Bone Morphogenetic Protein (bmp) Inhibition Mechanism Receptor Tyrosine Kinase Signal Transduction Transforming Growth Factor Β (tgf-b)
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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