Review Article
Open Access
Melatonin-Mediated Activation of the MKK5–MPK3/6 Cascade: A Molecular Framework for Integrated Drought Stress Tolerance in Plants
1
State Key Laboratory of Tree Genetics and Breeding, College of Life Sciences, Nanjing Forestry University, Nanjing 210037, China
* Corresponding Author:
Ali Movahedi,
[email protected]
Volume 1, Issue 1
2026
Received: 29 September 2025
Accepted: 31 March 2026
Published: 05 April 2026
Article Information
Abstract
Drought stress is one of the most devastating abiotic stresses threatening global food security. Melatonin (N-acetyl-5-methoxytryptamine) and Mitogen-Activated Protein Kinase Kinase 5 (MKK5) are independently recognized as central regulators of plant stress adaptation; however, the molecular intersection of their signaling axes remains poorly characterized. This review proposes and examines a coherent molecular framework wherein melatonin, perceived via the phytomelatonin receptor PMTR1/CAND2, may converge on MKK5-containing MPK3/6 signaling modules as part of a broader MKK4/5/7/9 MAPK response network to orchestrate an integrated drought stress response. Key convergence points include the ABA-AIK1-MKK5-MPK6 module, reactive oxygen species (ROS) homeostasis, cooperative stomatal regulation, and the shared transcriptional targeting of WRKY and DREB factors. Understanding this melatonin–MKK5 axis opens new avenues for engineering drought-resilient crops in the context of accelerating climate change.
Graphical Abstract
Keywords
melatonin
MKK5
MAPK cascade
PMTR1/CAND2
drought stress
Data Availability Statement
Not applicable.
Funding
This work was supported without any funding.
Conflicts of Interest
The authors declare no conflicts of interest.
AI Use Statement
The authors declare that no generative AI was used in the preparation of this manuscript.
Ethical Approval and Consent to Participate
Not applicable.
References
- Luo, C. K., Min, W. F., Akhtar, M., Lu, X. P., Bai, X. R., Zhang, Y. X., ... & Chen, X. H. (2022). Melatonin Enhances Drought Tolerance in Rice Seedlings by Modulating Antioxidant Systems, Osmoregulation, and Corresponding Gene Expression. International Journal of Molecular Sciences, 23(20), 12075.
[CrossRef] [Google Scholar] - Lee, H. Y., & Back, K. (2016). Mitogen-activated protein kinase pathways are required for melatonin-mediated defense responses in plants. Journal of Pineal Research, 60(3), 327–335.
[CrossRef] [Google Scholar] - Movahedi, A., Hwarari, D., Dzinyela, R., Ni, S. Y., & Yang, L. M. (2025). A close-up of regulatory networks and signaling pathways of MKK5 in biotic and abiotic stresses. Critical Reviews in Biotechnology, 45(2), 473–490.
[CrossRef] [Google Scholar] - Li, K., Yang, F. B., Zhang, G. Z., Song, S. F., Li, Y., Ren, D. T., ... & Xiong, L. M. (2017). AIK1, A Mitogen-Activated Protein Kinase, Modulates Abscisic Acid Responses through the MKK5-MPK6 Kinase Cascade. Plant Physiology, 173(2), 1391–1408.
[CrossRef] [Google Scholar] - Back, K., Tan, D. X., & Reiter, R. J. (2016). Melatonin biosynthesis in plants: multiple pathways catalyze tryptophan to melatonin in the cytoplasm or chloroplasts. Journal of Pineal Research, 61(4), 426–437.
[CrossRef] [Google Scholar] - Dzinyela, R., Hwarari, D., Opoku, K. N., Yang, L., & Movahedi, A. (2024). Enhancing drought stress tolerance in horticultural plants through melatonin-mediated phytohormonal crosstalk. Plant Cell Reports, 43(11), 272.
[CrossRef] [Google Scholar] - Li, C., Tan, D. X., Liang, D., Chang, C., Jia, D. F., & Ma, F. W. (2015). Melatonin mediates the regulation of ABA metabolism, free-radical scavenging, and stomatal behaviour in two Malus species under drought stress. Journal of Experimental Botany, 66(3), 669–680.
[CrossRef] [Google Scholar] - Wei, J., Li, D. X., Zhang, J. R., Shan, C., Rengel, Z., Song, Z. B., & Chen, Q. (2018). Phytomelatonin receptor PMTR1-mediated signaling regulates stomatal closure in Arabidopsis thaliana. Journal of Pineal Research, 65(2), e12500.
[CrossRef] [Google Scholar] - Lee, H. Y., & Back, K. (2017). Melatonin is required for H$_2$O$_2$- and NO-mediated defense signaling through MAPKKK3 and OXI1 in Arabidopsis thaliana. Journal of Pineal Research, 62(2), e12379.
[CrossRef] [Google Scholar] - Wang, L. F., Li, T. T., Zhang, Y., Guo, J. X., Lu, K. K., & Liu, W. C. (2021). CAND2/PMTR1 Is Required for Melatonin-Conferred Osmotic Stress Tolerance in Arabidopsis. International Journal of Molecular Sciences, 22(8), 4014.
[CrossRef] [Google Scholar] - Wang, L. F., Lu, K. K., Li, T. T., Zhang, Y., Guo, J. X., Song, R. F., & Liu, W. C. (2022). Maize PHYTOMELATONIN RECEPTOR1 functions in plant tolerance to osmotic and drought stress. Journal of Experimental Botany, 73(17), 5961–5973.
[CrossRef] [Google Scholar] - Ahn, H. R., Kim, Y. J., Lim, Y. J., Duan, S. C., Eom, S. H., & Jung, K. H. (2021). Key Genes in the Melatonin Biosynthesis Pathway with Circadian Rhythm Are Associated with Various Abiotic Stresses. Plants, 10(1), 129.
[CrossRef] [Google Scholar]
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APA Style
Movahedi, A., & Yang, L. (2026). Melatonin-Mediated Activation of the MKK5–MPK3/6 Cascade: A Molecular Framework for Integrated Drought Stress Tolerance in Plants. Plant Innovation Journal, 1(1), 50–57. https://doi.org/10.62762/PIJ.2026.832797
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TY - JOUR AU - Movahedi, Ali AU - Yang, Liming PY - 2026 DA - 2026/04/05 TI - Melatonin-Mediated Activation of the MKK5–MPK3/6 Cascade: A Molecular Framework for Integrated Drought Stress Tolerance in Plants JO - Plant Innovation Journal T2 - Plant Innovation Journal JF - Plant Innovation Journal VL - 1 IS - 1 SP - 50 EP - 57 DO - 10.62762/PIJ.2026.832797 UR - https://www.icck.org/article/abs/PIJ.2026.832797 KW - melatonin KW - MKK5 KW - MAPK cascade KW - PMTR1/CAND2 KW - drought stress AB - Drought stress is one of the most devastating abiotic stresses threatening global food security. Melatonin (N-acetyl-5-methoxytryptamine) and Mitogen-Activated Protein Kinase Kinase 5 (MKK5) are independently recognized as central regulators of plant stress adaptation; however, the molecular intersection of their signaling axes remains poorly characterized. This review proposes and examines a coherent molecular framework wherein melatonin, perceived via the phytomelatonin receptor PMTR1/CAND2, may converge on MKK5-containing MPK3/6 signaling modules as part of a broader MKK4/5/7/9 MAPK response network to orchestrate an integrated drought stress response. Key convergence points include the ABA-AIK1-MKK5-MPK6 module, reactive oxygen species (ROS) homeostasis, cooperative stomatal regulation, and the shared transcriptional targeting of WRKY and DREB factors. Understanding this melatonin–MKK5 axis opens new avenues for engineering drought-resilient crops in the context of accelerating climate change. SN - 3142-7596 PB - Institute of Central Computation and Knowledge LA - English ER -
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@article{Movahedi2026MelatoninM,
author = {Ali Movahedi and Liming Yang},
title = {Melatonin-Mediated Activation of the MKK5–MPK3/6 Cascade: A Molecular Framework for Integrated Drought Stress Tolerance in Plants},
journal = {Plant Innovation Journal},
year = {2026},
volume = {1},
number = {1},
pages = {50-57},
doi = {10.62762/PIJ.2026.832797},
url = {https://www.icck.org/article/abs/PIJ.2026.832797},
abstract = {Drought stress is one of the most devastating abiotic stresses threatening global food security. Melatonin (N-acetyl-5-methoxytryptamine) and Mitogen-Activated Protein Kinase Kinase 5 (MKK5) are independently recognized as central regulators of plant stress adaptation; however, the molecular intersection of their signaling axes remains poorly characterized. This review proposes and examines a coherent molecular framework wherein melatonin, perceived via the phytomelatonin receptor PMTR1/CAND2, may converge on MKK5-containing MPK3/6 signaling modules as part of a broader MKK4/5/7/9 MAPK response network to orchestrate an integrated drought stress response. Key convergence points include the ABA-AIK1-MKK5-MPK6 module, reactive oxygen species (ROS) homeostasis, cooperative stomatal regulation, and the shared transcriptional targeting of WRKY and DREB factors. Understanding this melatonin–MKK5 axis opens new avenues for engineering drought-resilient crops in the context of accelerating climate change.},
keywords = {melatonin, MKK5, MAPK cascade, PMTR1/CAND2, drought stress},
issn = {3142-7596},
publisher = {Institute of Central Computation and Knowledge}
}
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