ArticlePloS one2012
Human cataract mutations in EPHA2 SAM domain alter receptor stability and function.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Mutations in the EPHA2 gene are a major contributor to inherited cataracts in South-Eastern Australia.PloS one · 2013Trial
- Loss of ephrin-A5 leads to clinical signs of Peters Anomaly in a mouse model.Experimental eye research · 2026Article
- Frequent EPHA2 receptor mutations in cholangiocarcinoma disrupt receptor forward signaling supporting a tumor suppressor role.Biochimica et biophysica acta. Molecular cell research · 2026Article
- Eph-ephrin signaling affects lens growth and shape, nucleus size, and gradient refractive index in adult mice.Frontiers in ophthalmology · 2025Article
- Article
- Cancer-Related Mutations in the Sam Domains of EphA2 Receptor and Ship2 Lipid Phosphatase: A Computational Study.Molecules (Basel, Switzerland) · 2024Article
- EPHA2 Receptor as a Possible Therapeutic Target in Viral Infections.Current medicinal chemistry · 2024Review
- Abnormal function ofInternational journal of ophthalmology · 2024Article
- Article
- Ligands with different dimeric configurations potently activate the EphA2 receptor and reveal its potential for biased signaling.iScience · 2022Article
- EphA2 Affects Development of the Eye Lens Nucleus and the Gradient of Refractive Index.Investigative ophthalmology & visual science · 2022Article
- Roles of Eph-Ephrin Signaling in the Eye Lens Cataractogenesis, Biomechanics, and Homeostasis.Frontiers in cell and developmental biology · 2022Review
- Article
- Functional analysis of deleteriousMolecular vision · 2021Article
- Functional analysis of deleteriousMolecular vision · 2021Article
- DLC1 SAM domain-binding peptides inhibit cancer cell growth and migration by inactivating RhoA.The Journal of biological chemistry · 2020Article
- Making Connections: Guidance Cues and Receptors at Nonneural Cell-Cell Junctions.Cold Spring Harbor perspectives in biology · 2018Review
- EphA2 and ephrin-A5 are not a receptor-ligand pair in the ocular lens.Experimental eye research · 2017Article
- Screening, genetics, risk factors, and treatment of neonatal cataracts.Birth defects research · 2017Review
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The cellular and molecular mechanisms underlying the pathogenesis of cataracts leading to visual impairment remain poorly understood. In recent studies, several mutations in the cytoplasmic sterile-α-motif (SAM) domain of human EPHA2 on chromosome 1p36 have been associated with hereditary cataracts in several families. Here, we have investigated how these SAM domain mutations affect EPHA2 activity. We showed that the SAM domain mutations dramatically destabilized the EPHA2 protein in a proteasome-dependent pathway, as evidenced by the increase of EPHA2 receptor levels in the presence of the proteasome inhibitor MG132. In addition, the expression of wild-type EPHA2 promoted the migration of the mouse lens epithelial αTN4-1 cells in the absence of ligand stimulation, whereas the mutants exhibited significantly reduced activity. In contrast, stimulation of EPHA2 with its ligand ephrin-A5 eradicates the enhancement of cell migration accompanied by Akt activation. Taken together, our studies suggest that the SAM domain of the EPHA2 protein plays critical roles in enhancing the stability of EPHA2 by modulating the proteasome-dependent process. Furthermore, activation of Akt switches EPHA2 from promoting to inhibiting cell migration upon ephrin-A5 binding. Our results provide the first report of multiple EPHA2 cataract mutations contributing to the destabilization of the receptor and causing the loss of cell migration activity.
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Registered trials
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.