ArticleMolecular and cellular biology2015
Axl phosphorylates Elmo scaffold proteins to promote Rac activation and cell invasion.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 71 citations in OpenAlex.
- ELMO1 dependent efferocytosis protects from nephrotoxin induced acute kidney injury.Cell death discovery · 2026Article
- Implications of Heterotypic Cell Fusion in Cancer.Advances in experimental medicine and biology · 2026Review
- ELMO2 is an essential regulator of carotid artery development.Nature communications · 2025Article
- Recent advances in TAM mechanisms in lung diseases.Journal of translational medicine · 2025Review
- Mechanisms of Cell Fusion in Cancer.Results and problems in cell differentiation · 2024Review
- Gas6 Promotes Microglia Efferocytosis and Suppresses Inflammation Through Activating Axl/Rac1 Signaling in Subarachnoid Hemorrhage Mice.Translational stroke research · 2023Article
- Apoptotic cell clearance components in inflammatory arthritis.Immunological reviews · 2023Review
- CNK2 promotes cancer cell motility by mediating ARF6 activation downstream of AXL signalling.Nature communications · 2023Article
- AXL Inhibitors: Status of Clinical Development.Current oncology reports · 2023Review
- Structural biology of DOCK-family guanine nucleotide exchange factors.FEBS letters · 2023Review
- Role of ELMO1 in inflammation and cancer-clinical implications.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- DOCK4 Regulation of Rho GTPases Mediates Pulmonary Vascular Barrier Function.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- Review
- FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma.Cell reports · 2021Article
- Physiological Roles of Apoptotic Cell Clearance: Beyond Immune Functions.Life (Basel, Switzerland) · 2021Review
- AXL Receptor in Cancer Metastasis and Drug Resistance: When Normal Functions Go Askew.Cancers · 2021Review
- Fe65: A Scaffolding Protein of Actin Regulators.Cells · 2021Review
- AXL Is a Potential Target for the Treatment of Intestinal Fibrosis.Inflammatory bowel diseases · 2021Article
- AXL confers cell migration and invasion by hijacking a PEAK1-regulated focal adhesion protein network.Nature communications · 2020Article
- Structure of the DOCK2-ELMO1 complex provides insights into regulation of the auto-inhibited state.Nature communications · 2020Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The receptor tyrosine kinase Axl contributes to cell migration and invasion. Expression of Axl correlates with metastatic progression in cancer patients, yet the specific signaling events promoting invasion downstream of Axl are poorly defined. Herein, we report Elmo scaffolds to be direct substrates and binding partners of Axl. Elmo proteins are established to interact with Dock family guanine nucleotide exchange factors to control Rac-mediated cytoskeletal dynamics. Proteomics and mutagenesis studies reveal that Axl phosphorylates Elmo1/2 on a conserved carboxyl-terminal tyrosine residue. Upon Gas6-dependent activation of Axl, endogenous Elmo2 becomes phosphorylated on Tyr-713 and enters into a physical complex with Axl in breast cancer cells. Interfering with Elmo2 expression prevented Gas6-induced Rac1 activation in breast cancer cells. Similarly to blocking of Axl, Elmo2 knockdown or pharmacological inhibition of Dock1 abolishes breast cancer cell invasion. Interestingly, Axl or Elmo2 knockdown diminishes breast cancer cell proliferation. Rescue of Elmo2 knockdown cells with the wild-type protein but not with Elmo2 harboring Tyr-713-Phe mutations restores cell invasion and cell proliferation. These results define a new mechanism by which Axl promotes cell proliferation and invasion and identifies inhibition of the Elmo-Dock pathway as a potential therapeutic target to stop Axl-induced metastases.
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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.