API

Relationship: 2078

Title

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Increase, Cripto-1 expression leads to Inhibition, Activin signaling

Upstream event

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Increase, Cripto-1 expression

Downstream event

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Inhibition, Activin signaling

Key Event Relationship Overview

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AOPs Referencing Relationship

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AOP Name Adjacency Weight of Evidence Quantitative Understanding
Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration adjacent Moderate

Taxonomic Applicability

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Term Scientific Term Evidence Link
zebrafish Danio rerio Moderate NCBI

Sex Applicability

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Life Stage Applicability

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Term Evidence
larvae Moderate

Key Event Relationship Description

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Evidence Supporting this KER

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Biological Plausibility

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Empirical Evidence

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  • Transfection of HepG2 cells with Cripto results in a significant decrease in Activin-A signaling compared to cells transfected with an empty vector. It is believed that Cripto is able to form a complex with the alk4 receptor, blocking activin signaling. (Gray et al., 2003).

Uncertainties and Inconsistencies

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Due to a lack of evidence for different life stages, increases in cripto-1 expression can only be assumed in larval fish.

Quantitative Understanding of the Linkage

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Response-response Relationship

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Time-scale

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Known modulating factors

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Known Feedforward/Feedback loops influencing this KER

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Domain of Applicability

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References

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Gray PC, Harrison CA, Vale W. 2003. Cripto forms a complex with activin and type II activin receptors and can block activin signaling. Proceedings of the National Academy of Sciences of the United States of America 100(9):5193-5198. www.pnas.org/cgi/doi/10.1073/pnas.0531290100