ArticleProceedings of the National Academy of Sciences of the United States of America2015
Gαi1 and Gαi3 regulate macrophage polarization by forming a complex containing CD14 and Gab1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- FSTL4 interaction with Gαi proteins activates the Akt-mTOR pathway to drive malignant phenotypes in non-small cell lung cancer.Cell communication and signaling : CCS · 2026Article
- Gαi1/3 Is a Novel Regulatory Target for RANKL Signal Transduction and Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sensing succinate: SUCNR1 as a context-dependent metabolic and cellular signal integrator.Frontiers in molecular biosciences · 2026Review
- Endothelial RAB5IF is required for pathological and developmental retinal angiogenesis.Nature communications · 2025Article
- Gap junction protein beta 5 interacts with Gαi3 to promote Akt activation and cervical cancer cell growth.Cell death & disease · 2025Article
- Gαi3: a crucial biomarker and therapeutic target in bladder cancer.NPJ precision oncology · 2025Article
- RGS2 is an innate immune checkpoint for suppressing Gαq-mediated IFNγ generation and lung injury.iScience · 2025Article
- Activation of cellular responses by cyclic dinucleotides andJournal of oral microbiology · 2025Article
- Immunotherapy against colorectal cancer via delivery of anti-PD-L1 nanobody mRNA.eGastroenterology · 2025Article
- Regulation of RSPO3-LGR4 Signaling: Emerging Role in Inflammation Revealed by Network Analysis.Archives of clinical and biomedical research · 2025Article
- The critical role of Gαi3 in oral squamous cell carcinoma cell growth.Cell death discovery · 2024Article
- Targeting the mitochondrial protein YME1L to inhibit osteosarcoma cell growth in vitro and in vivo.Cell death & disease · 2024Article
- Expression and functional significance of phosphoenolpyruvate carboxykinase 1 in uveal melanoma.Cell death discovery · 2024Article
- Gαi1/3 signaling mediates IL-5-induced eosinophil activation and type 2 inflammation in eosinophilic chronic rhinosinusitis.Frontiers in immunology · 2024Article
- G protein subunit alpha i2's pivotal role in angiogenesis.Theranostics · 2024Article
- Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinoma.Cell death & disease · 2023Article
- Endothelial cell-derived RSPO3 activates Gαi1/3-Erk signaling and protects neurons from ischemia/reperfusion injury.Cell death & disease · 2023Article
- Target and Cell Therapy for Atherosclerosis and CVD.International journal of molecular sciences · 2023Review
- Gαi1/3 mediate Netrin-1-CD146-activated signaling and angiogenesis.Theranostics · 2023Article
- SCF/c-Kit-activated signaling and angiogenesis require Gαi1 and Gαi3.International journal of biological sciences · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 8 institutions in 2 countries.
Funding
Abstract
Heterotrimeric G proteins have been implicated in Toll-like receptor 4 (TLR4) signaling in macrophages and endothelial cells. However, whether guanine nucleotide-binding protein G(i) subunit alpha-1 and alpha-3 (Gαi1/3) are required for LPS responses remains unclear, and if so, the underlying mechanisms need to be studied. In this study, we demonstrated that, in response to LPS, Gαi1/3 form complexes containing the pattern recognition receptor (PRR) CD14 and growth factor receptor binding 2 (Grb2)-associated binding protein (Gab1), which are required for activation of PI3K-Akt signaling. Gαi1/3 deficiency decreased LPS-induced TLR4 endocytosis, which was associated with decreased phosphorylation of IFN regulatory factor 3 (IRF3). Gαi1/3 knockdown in bone marrow-derived macrophage cells (Gαi1/3 KD BMDMs) exhibited an M2-like phenotype with significantly suppressed production of TNF-α, IL-6, IL-12, and NO in response to LPS. The altered polarization coincided with decreased Akt activation. Further, Gαi1/3 deficiency caused LPS tolerance in mice. In vitro studies revealed that, in LPS-tolerant macrophages, Gαi1/3 were down-regulated partially by the proteasome pathway. Collectively, the present findings demonstrated that Gαi1/3 can interact with CD14/Gab1, which modulates macrophage polarization in vitro and in vivo.
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