NodalとActivinは「同じ」受容体を使うが、完全に同一ではありません

受容体の共通性と違い

NodalとActivinはどちらもTGF-βスーパーファミリーに属し、シグナル伝達には「アクチビン型I型（ALK4, ALK7）およびII型（ActRIIA, ActRIIB）」セリン/スレオニンキナーゼ受容体を共有します (Reissmann et al., 2001; Tsuchida et al., 2008; Preiß et al., 2022; Lee et al., 2011; Tsuchida et al., 2009; Nadeem et al., 2011; Miles et al., 2013)。

• Activin：主にALK4（ACVR1B）とActRIIA/ActRIIBを利用し、コレセプター（Criptoなど）は不要です (Gray et al., 2003; Lee et al., 2011; Tsuchida et al., 2009)。
• Nodal：ALK4またはALK7とActRIIB（主に）を利用しますが、CriptoなどEGF-CFCファミリーのコレセプターが必須です (Reissmann et al., 2001; Preiß et al., 2022; Gray et al., 2003; Lee et al., 2011; Tsuchida et al., 2009; Nadeem et al., 2011)。

分子機構の違い

• NodalはCriptoなどのコレセプターがなければ受容体複合体を形成できませんが、ActivinはCriptoなしで直接受容体複合体を形成しシグナルを伝達できます (Gray et al., 2003; Lee et al., 2011; Tsuchida et al., 2009)。
• ALK7はNodalに対してより特異的なI型受容体であり、Activinは主にALK4を介して作用しますが、両者ともALK4/ALK7とActRIIA/ActRIIBの組み合わせでシグナルを伝達できます (Reissmann et al., 2001; Tsuchida et al., 2008; Preiß et al., 2022; Tsuchida et al., 2009; Nadeem et al., 2011; Miles et al., 2013)。

受容体利用のまとめ

Figure 1: NodalとActivinの受容体利用の比較表

結論

NodalとActivinは「アクチビン型I型・II型受容体」を共有しますが、Nodalはコレセプター（Cripto等）が必須であり、受容体利用やシグナル伝達の詳細に違いがあります。完全に同一の分子機構ではありませんが、受容体の主要部分は共通です。

These papers were sourced and synthesized using Consensus, an AI-powered search engine for research. Try it at https://consensus.app

References

Reissmann, E., Jörnvall, H., Blokzijl, A., Andersson, O., Chang, C., Minchiotti, G., Persico, M., Ibáñez, C., & Brivanlou, A. (2001). The orphan receptor ALK7 and the Activin receptor ALK4 mediate signaling by Nodal proteins during vertebrate development.. Genes & development, 15 15, 2010-22. https://doi.org/10.1101/gad.201801

Tsuchida, K., Nakatani, M., Uezumi, A., Murakami, T., & Cui, X. (2008). Signal transduction pathway through activin receptors as a therapeutic target of musculoskeletal diseases and cancer.. Endocrine journal, 55 1, 11-21. https://doi.org/10.1507/endocrj.kr-110

Preiß, H., Kögler, A., Mörsdorf, D., Čapek, D., Soh, G., Rogers, K., Morales-Navarrete, H., Almuedo-Castillo, M., & Müller, P. (2022). Regulation of Nodal signaling propagation by receptor interactions and positive feedback. eLife, 11. https://doi.org/10.7554/elife.66397

Gray, P., Harrison, C., & 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, 5193 – 5198. https://doi.org/10.1073/pnas.0531290100

Lee, K., Lim, S., Orlov, Y., Yit, L., Yang, H., Ang, L., Poellinger, L., & Lim, B. (2011). Graded Nodal/Activin Signaling Titrates Conversion of Quantitative Phospho-Smad2 Levels into Qualitative Embryonic Stem Cell Fate Decisions. PLoS Genetics, 7. https://doi.org/10.1371/journal.pgen.1002130

Tsuchida, K., Nakatani, M., Hitachi, K., Uezumi, A., Sunada, Y., Ageta, H., & Inokuchi, K. (2009). Activin signaling as an emerging target for therapeutic interventions. Cell Communication and Signaling : CCS, 7, 15 – 15. https://doi.org/10.1186/1478-811x-7-15

Nadeem, L., Munir, S., Fu, G., Dunk, C., Baczyk, D., Caniggia, I., Lye, S., & Peng, C. (2011). Nodal signals through activin receptor-like kinase 7 to inhibit trophoblast migration and invasion: implication in the pathogenesis of preeclampsia.. The American journal of pathology, 178 3, 1177-89. https://doi.org/10.1016/j.ajpath.2010.11.066

Miles, D., Wakeling, S., Stringer, J., Van Den Bergen, J., Wilhelm, D., Sinclair, A., & Western, P. (2013). Signaling through the TGF Beta-Activin Receptors ALK4/5/7 Regulates Testis Formation and Male Germ Cell Development. PLoS ONE, 8. https://doi.org/10.1371/journal.pone.0054606

(Consensus)