Cripto forms a complex with activin and type II activin receptors and can block activin signaling

Gray, Peter C.; Harrison, Craig A.; Vale, Wylie

doi:10.1073/pnas.0531290100

Cited by 146 publications

(136 citation statements)

References 48 publications

Supporting

Mentioning

126

Contrasting

Order By: Relevance

“…Thus, different type II and type I receptors must combine with each other to produce functional receptor complexes with a range of specificities to accommodate this diversity of ligands. Receptor complex specificity can also be altered through accessory proteins such as Cripto, which suppress binding of activin to ActRII and promote nodal binding (33). In this regard, activin type II receptors are a particularly interesting example of promiscuity within this family since they participate in signal transduction for activins, myostatin, nodal, and certain bone morphogenetic proteins (BMPs) through alterations in their complex partners (15,34).…”

Section: Fig 2 Representative Binding Results and Scatchard Analysimentioning

confidence: 99%

Reconstitution and Analysis of Soluble Inhibin and Activin Receptor Complexes in a Cell-free System

Re¹,

Sidis

Fabrizio³

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Activins and inhibins compose a heterogeneous subfamily within the transforming growth factor-␤ (TGF-␤) superfamily of growth and differentiation factors with critical biological activities in embryos and adults. They signal through a heteromeric complex of type II, type I, and for inhibin, type III receptors. To characterize the affinity, specificity, and activity of these receptors (alone and in combination) for the inhibin/activin subfamily, we developed a cell-free assay system using soluble receptor-Fc fusion proteins. The soluble activin type II receptor (sActRII)-Fc fusion protein had a 7-fold higher affinity for activin A compared with sActRIIB-Fc, whereas both receptors had a marked preference for activin A over activin B. Although inhibin A and B binding was 20-fold lower compared with activin binding to either type II receptor alone, the mixture of either type II receptor with soluble TGF-␤ type III receptor (T␤RIII; betaglycan)-Fc reconstituted a soluble high affinity inhibin receptor. In contrast, mixing either soluble activin type II receptor with soluble activin type I receptors did not substantially enhance activin binding. Our results support a cooperative model of binding for the inhibin receptor (ActRII⅐sT␤RIII complex) but not for activin receptors (type II ؉ type I) and demonstrate that a complex composed of activin type II receptors and T␤RIII is both necessary and sufficient for high affinity inhibin binding. This study also illustrates the utility of this cell-free system for investigating hypotheses of receptor complex mechanisms resulting from crystal structure analyses.

show abstract

Section: Fig 2 Representative Binding Results and Scatchard Analysimentioning

confidence: 99%

Reconstitution and Analysis of Soluble Inhibin and Activin Receptor Complexes in a Cell-free System

Re¹,

Sidis

Fabrizio³

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Activin is however antagonized by another secreted molecule, called Follistatin. There is also evidence that Cripto can inhibit signalling from Activin, TGF-b and Myostatin, which have in common to signal via Smad2/3 without requiring an EGF-CFC co-receptor to interact with their receptor complex [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Activin/Nodal signalling before implantation: setting the stage for embryo patterning

Papanayotou

Collignon

2014

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

Activins and Nodal are members of the transforming growth factor beta (TGF-b) family of growth factors. Their Smad2/3-dependent signalling pathway is well known for its implication in the patterning of the embryo after implantation. Although this pathway is active early on at preimplantation stages, embryonic phenotypes for loss-of-function mutations of prominent components of the pathway are not detected before implantation. It is only fairly recently that an understanding of the role of the Activin/Nodal signalling pathway at these stages has started to emerge, notably from studies detailing how it controls the expression of target genes in embryonic stem cells. We review here what is currently known of the TGF-b-related ligands that determine the activity of Activin/Nodal signalling at preimplantation stages, and recent advances in the elucidation of the Smad2/3-dependent mechanisms underlying developmental progression.

show abstract

“…In contrast to its coreceptor function, Cripto is able to antagonize signaling of other members of the TGF-β family (i.e., activins and TGF-β). This inhibitory activity of Cripto results in a reduced ability to form an active ActRII/ActRIB receptor complex (13)(14)(15).…”

mentioning

confidence: 99%

Cripto regulates skeletal muscle regeneration and modulates satellite cell determination by antagonizing myostatin

Guardiola

Lafuste

Brunelli

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Skeletal muscle regeneration mainly depends on satellite cells, a population of resident muscle stem cells. However, our understanding of the molecular mechanisms underlying satellite cell activation is still largely undefined. Here, we show that Cripto, a regulator of early embryogenesis, is a novel regulator of muscle regeneration and satellite cell progression toward the myogenic lineage. Conditional inactivation of cripto in adult satellite cells compromises skeletal muscle regeneration, whereas gain of function of Cripto accelerates regeneration, leading to muscle hypertrophy. Moreover, we provide evidence that Cripto modulates myogenic cell determination and promotes proliferation by antagonizing the TGF-β ligand myostatin. Our data provide unique insights into the molecular and cellular basis of Cripto activity in skeletal muscle regeneration and raise previously undescribed implications for stem cell biology and regenerative medicine. myogenic commitment | skeletal muscle stem cells | teratocarcinoma derived growth factor-1 (TDGF-1) | growth differentiation factor-8 (GDF-8)

show abstract

Cripto forms a complex with activin and type II activin receptors and can block activin signaling

Cited by 146 publications

References 48 publications

Reconstitution and Analysis of Soluble Inhibin and Activin Receptor Complexes in a Cell-free System

Reconstitution and Analysis of Soluble Inhibin and Activin Receptor Complexes in a Cell-free System

Activin/Nodal signalling before implantation: setting the stage for embryo patterning

Cripto regulates skeletal muscle regeneration and modulates satellite cell determination by antagonizing myostatin

Contact Info

Product

Resources

About