ArticleJournal of cell science2018
Stress-activated MAPKs and CRM1 regulate the subcellular localization of Net1A to control cell motility and invasion.
Article in Journal of cell science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- MLC2: Physiological Functions and Potential Roles in Tumorigenesis.Cell biochemistry and biophysics · 2025Review
- Invadopodia in cancer metastasis: dynamics, regulation, and targeted therapies.Journal of translational medicine · 2025Review
- Multiomics analysis reveals the involvement of NET1 in tumour immune regulation and malignant progression.Scientific reports · 2025Article
- Targeting radiotherapy-induced inflammation in cancer metastasis: insights into immune modulation, therapeutic opportunities and radiogenomics.Frontiers in oncology · 2025Review
- ERK/CREB and p38 MAPK/MMP14 Signaling Pathway Influences Spermatogenesis through Regulating the Expression of Junctional Proteins inInternational journal of molecular sciences · 2024Article
- Neuroepithelial cell-transforming 1 promotes cardiac fibrosis via the Wnt/β-catenin signaling pathway.iScience · 2023Article
- mRNA location and translation rate determine protein targeting to dual destinations.Molecular cell · 2023Article
- Src stimulates Abl-dependent phosphorylation of the guanine exchange factor Net1A to promote its cytosolic localization and cell motility.The Journal of biological chemistry · 2023Article
- mRNA Location and Translation Rate Determine Protein Targeting to Dual Destinations.bioRxiv : the preprint server for biology · 2023Article
- Cytoskeleton and Associated Proteins: Pleiotropic JNK Substrates and Regulators.International journal of molecular sciences · 2021Review
- Role of Small GTPase RhoA in DNA Damage Response.Biomolecules · 2021Review
- Regulation of RhoA activation and cell motility by c-Jun N-terminal kinases and Net1.Small GTPases · 2020Article
- Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The neuroepithelial cell transforming gene 1A (Net1A, an isoform of Net1) is a RhoA subfamily guanine nucleotide exchange factor (GEF) that localizes to the nucleus in the absence of stimulation, preventing it from activating RhoA. Once relocalized in the cytosol, Net1A stimulates cell motility and extracellular matrix invasion. In the present work, we investigated mechanisms responsible for the cytosolic relocalization of Net1A. We demonstrate that inhibition of MAPK pathways blocks Net1A relocalization, with cells being most sensitive to JNK pathway inhibition. Moreover, activation of the JNK or p38 MAPK family pathway is sufficient to elicit Net1A cytosolic localization. Net1A relocalization stimulated by EGF or JNK activation requires nuclear export mediated by CRM1. JNK1 (also known as MAPK8) phosphorylates Net1A on serine 52, and alanine substitution at this site prevents Net1A relocalization caused by EGF or JNK activation. Glutamic acid substitution at this site is sufficient for Net1A relocalization and results in elevated RhoA signaling to stimulate myosin light chain 2 (MLC2, also known as MYL2) phosphorylation and F-actin accumulation. Net1A S52E expression stimulates cell motility, enables Matrigel invasion and promotes invadopodia formation. These data highlight a novel mechanism for controlling the subcellular localization of Net1A to regulate RhoA activation, cell motility, and invasion.
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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.