ArticleProceedings of the National Academy of Sciences of the United States of America2011
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) integrates developmental signals for eyelid closure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 43 citations in OpenAlex.
- Receptor tyrosine kinase signaling in mammalian eye development.Developmental biology · 2026Review
- Review
- AP1 Transcription Factor in the Regulation of the Urokinase Plasminogen Activation System.Biomolecules · 2026Review
- MAP3K1: A Multifunctional Kinase at the Crossroads of Cancer Progression and Tumor Suppression.Cells · 2026Review
- Functions of RhoA in the female reproductive system.Reproductive and developmental medicine · 2025Review
- Inhibin subunit beta B (INHBB): an emerging role in tumor progression.Journal of physiology and biochemistry · 2024Review
- Crosstalk of MAP3K1 and EGFR signaling mediates gene-environment interactions that block developmental tissue closure.The Journal of biological chemistry · 2024Article
- Review
- An L314Q mutation in Map3k1 gene results in failure of eyelid fusion in the N-ethyl-N-nitrosourea-induced mutant line.Experimental animals · 2021Article
- Novel compound variants of the AR and MAP3K1 genes are related to the clinical heterogeneity of androgen insensitivity syndrome.Bioscience reports · 2020Article
- A C1976Y missense mutation in the mouse Ip3r1 gene leads to short-term mydriasis and unfolded protein response in the iris constrictor muscles.Experimental animals · 2020Article
- Repression of MAP3K1 expression and JNK activity by canonical Wnt signaling.Developmental biology · 2018Article
- "Positive Regulation of RNA Metabolic Process" Ontology Group Highly Regulated in Porcine Oocytes MaturedBioMed research international · 2018Article
- In Vivo Rescue Assay of RhoA-Deficient Hematopoietic Stem and Progenitor Cells.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Role of EGF receptor signaling on morphogenesis of eyelid and meibomian glands.Experimental eye research · 2017Review
- Meibomian gland morphogenesis requires developmental eyelid closure and lid fusion.The ocular surface · 2017Article
- Magnetic resonance imaging study of eye congenital birth defects in mouse model.Molecular vision · 2017Article
- Oleanolic acid induces migration in Mv1Lu and MDA-MB-231 epithelial cells involving EGF receptor and MAP kinases activation.PloS one · 2017Article
- Meta-Analysis of Gene Expression Profiles in Acute Promyelocytic Leukemia Reveals Involved Pathways.International journal of hematology-oncology and stem cell research · 2017Article
- Loss of IκB kinase β promotes myofibroblast transformation and senescence through activation of the ROS-TGFβ autocrine loop.Protein & cell · 2016Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
Abstract
Developmental eyelid closure is an evolutionarily conserved morphogenetic event requiring proliferation, differentiation, cytoskeleton reorganization, and migration of epithelial cells at the tip of the developing eyelid. Many signaling events take place during eyelid closure, but how the signals converge to regulate the morphogenetic process remains an open and intriguing question. Here we show that mitogen-activated protein kinase kinase kinase 1 (MAP3K1) highly expressed in the developing eyelid epithelium, forms with c-Jun, a regulatory axis that orchestrates morphogenesis by integrating two different networks of eyelid closure signals. A TGF-α/EGFR-RhoA module initiates one of these networks by inducing c-Jun expression which, in a phosphorylation-independent manner, binds to the Map3k1 promoter and causes an increase in MAP3K1 expression. RhoA knockout in the ocular surface epithelium disturbs this network by decreasing MAP3K1 expression, and causes delayed eyelid closure in Map3k1 hemizygotes. The second network is initiated by the enzymatic activity of MAP3K1, which phosphorylates and activates a JNK-c-Jun module, leading to AP-1 transactivation and induction of its downstream genes, such as Pai-1. MAP3K1 inactivation reduces AP-1 activity and PAI-1 expression both in cells and developing eyelids. MAP3K1 is therefore the nexus of an intracrine regulatory loop connecting the TGF-α/EGFR/RhoA-c-Jun and JNK-c-Jun-AP-1 pathways in developmental eyelid closure.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.