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Relationship: 2078
Title
Increase, Cripto-1 expression leads to Inhibition, Activin signaling
Upstream event
Downstream event
Key Event Relationship Overview
AOPs Referencing Relationship
AOP Name | Adjacency | Weight of Evidence | Quantitative Understanding | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|---|---|
Glucocorticoid Receptor Agonism Leading to Impaired Fin Regeneration | adjacent | Moderate | Brendan Ferreri-Hanberry (send email) | Open for citation & comment |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
---|---|---|---|
zebrafish | Danio rerio | Moderate | NCBI |
Sex Applicability
Life Stage Applicability
Term | Evidence |
---|---|
Larvae | Moderate |
Key Event Relationship Description
Cripto-1 is responsible for growth factor activity, as well as activin binding on the cell membrane. Cripto-1 may also be referred to as teratocarcinoma-derived growth factor 1, tdgf1, or one-eyed pinhead protein, depending on the species (Uniprot).
Uniprot ID
Activin is a dimeric protein composed of two β subunits. These subunits – either βA or βB – dictate the specific type of activin depending on their pairing. Activins have different function depending on the tissue in which they are acting (Kaneko, 2016) Activin plays a large role in cancer metastasis, immune response, inflammation and cell migration (Kang & Shyr, 2011). In fish, the activin signaling pathway is involved with the promotion of blastemal cell proliferation in the fin regeneration process (Wehner & Weidinger, 2015).
Evidence Collection Strategy
Evidence Supporting this KER
Biological Plausibility
Empirical Evidence
- 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
Due to a lack of evidence for different life stages, increases in cripto-1 expression can only be assumed in larval fish.
Known modulating factors
Not yet evaluated.
Quantitative Understanding of the Linkage
Not yet evaluated.
Response-response Relationship
Not yet evaluated.
Time-scale
Not yet evaluated.
Known Feedforward/Feedback loops influencing this KER
Not yet evaluated.
Domain of Applicability
Cripto-1 expression has been seen in Zebrafish (Danio rerio) Sengupta et al., 2012). Additionally, cripto-1 is a known activin inhibitor (Sengupta et al., 2012). The limits of cripto-1's ability to inhibit activin signalling in different species is currently unknown.
References
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