ArticleFrontiers in immunology2017
Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6.
Article in Frontiers in immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- The Multifaceted Roles of TAM Receptors during Viral Infection.Virologica Sinica · 2021Pooled it
- Structural organization of TAM receptor ectodomains.The Biochemical journal · 2026Article
- AXL at the nexus of therapeutic resistance, tumor vascularization, and immune evasion in cancer.iScience · 2026Review
- Structural basis of phosphatidylserine enhancement of Gas6 ligand-induced Axl activation.bioRxiv : the preprint server for biology · 2026Article
- TAM receptor tyrosine kinases as potential mediators of the non-lytic spread of non-enveloped viruses.Biochemical Society transactions · 2026Review
- Macrophage efferocytosis promotes inflammation resolution and accelerates wound healing.Communications biology · 2026Review
- Review
- Multiomics Integration Analysis Reveals the Regulatory Mechanisms of Efferocytosis in Diabetic Kidney Disease.Inflammation · 2026Article
- Article
- Advancements in nanomedicine for the therapeutic regulation of efferocytosis: opportunities and challenges.Theranostics · 2026Review
- Efferocytosis in heart failure: Mechanisms, dysregulation and therapeutic potential.Theranostics · 2026Review
- Preclinical evaluation of CPL423: a novel potent small-molecule inhibitor of TAM family and FLT3 kinase for cancer therapy.Frontiers in pharmacology · 2026Article
- From pathogenesis to therapeutic targeting: new insight into TAM receptors in rheumatoid arthritis.Cell & bioscience · 2025Review
- Heterogeneity of Lung Phagocytes and Clearance of Apoptotic Cells in Lung Injury and Repair.Seminars in respiratory and critical care medicine · 2025Review
- Screen of FDA-approved drug library identifies vitamin K as anti-ferroptotic drug for osteoarthritis therapy through Gas6.Journal of pharmaceutical analysis · 2025Article
- Navigating TAM receptor dynamics in tumour immunotherapy.Cancer immunology, immunotherapy : CII · 2025Review
- Dys-regulated phosphatidylserine externalization as a cell intrinsic immune escape mechanism in cancer.Cell communication and signaling : CCS · 2025Review
- Efferocytosis: The Janus-Faced Gatekeeper of Aging and Tumor Fate.Aging cell · 2025Review
- Phosphatidylserine (PS)-targeting chimeric Interferon (IFN) fusion proteins for anti-tumor applications.bioRxiv : the preprint server for biology · 2025Article
- Establishing Tyro3, Axl, and Mertk Chinese hamster ovary (CHO) reporter cell lines for cancer immunology and therapeutic applications.Methods in cell biology · 2025Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The Tyro3, Axl, and Mertk (TAM) receptors are homologous type I receptor tyrosine kinases that have critical functions in the clearance of apoptotic cells in multicellular organisms. TAMs are activated by their endogenous ligands, growth arrest-specific 6 (Gas6), and protein S (Pros1), that function as bridging molecules between externalized phosphatidylserine (PS) on apoptotic cells and the TAM ectodomains. However, the molecular mechanisms by which Gas6/Pros1 promote TAM activation remains elusive. Using TAM/IFNγR1 reporter cell lines to monitor functional TAM activity, we found that Gas6 activity was exquisitely dependent on vitamin K-mediated γ-carboxylation, whereby replacing vitamin K with anticoagulant warfarin, or by substituting glutamic acid residues involved in PS binding, completely abrogated Gas6 activity as a TAM ligand. Furthermore, using domain and point mutagenesis, Gas6 activity also required both an intact Gla domain and intact EGF-like domains, suggesting these domains function cooperatively in order to achieve TAM activation. Despite the requirement of γ-carboxylation and the functional Gla domain, non-γ-carboxylated Gas6 and Gla deletion/EGF-like domain deletion mutants still retained their ability to bind TAMs and acted as blocking decoy ligands. Finally, we found that distinct sources of PS-positive cells/vesicles (including apoptotic cells, calcium-induced stressed cells, and exosomes) bound Gas6 and acted as cell-derived or exosome-derived ligands to activate TAMs. Taken together, our findings indicate that PS is indispensable for TAM activation by Gas6, and by inference, provides new perspectives on how PS, regulates TAM receptors and efferocytosis.
Indexed as
Identifiers
What OpenQuestion holds
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.