ArticleMolecular and cellular biology2006
RACK1 recruits STAT3 specifically to insulin and insulin-like growth factor 1 receptors for activation, which is important for regulating anchorage-independent growth.
Article in Molecular and cellular biology, 2006. 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 74 papers.
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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.
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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.
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Who cites it
74 citing papers in PubMed, 118 citations in OpenAlex.
- Neutrophil Mechanosignaling Promotes Integrin Engagement With Endothelial Cells and Motility Within Inflamed Vessels.Frontiers in immunology · 2018Trial
- SMYD3 synergises with RACK1 to promote colorectal cancer lung metastasis by recruiting SMAD3.Cell communication and signaling : CCS · 2026Article
- A Duality of Function: An Integrative Model of RACK1 as a Switch Between Translational and Signaling Hubs.International journal of molecular sciences · 2025Review
- RACK1 promotes the development and function of alveolar macrophages through directly binding to and stabilizing PPARγ.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- IGF1R Enhances Calcium Oxalate Monohydrate-Induced Epithelial-Mesenchymal Transition by Reprogramming Metabolism via the JAK2/STAT3 Signaling.International journal of biological sciences · 2025Article
- Rack1 regulates B-cell development and function by binding to and stabilizing the transcription factor Pax5.Cellular & molecular immunology · 2024Article
- Tumor-associated macrophages/C-X-C motif chemokine ligand 1 promotes breast cancer autophagy-mediated chemoresistance via IGF1R/STAT3/HMGB1 signaling.Cell death & disease · 2024Article
- Role of Insulin-like Growth Factor-1 Receptor in Tobacco Smoking-Associated Lung Cancer Development.Biomedicines · 2024Review
- Inhibition of insulin-like growth factors increases production of CXCL9/10 by macrophages and fibroblasts and facilitates CD8Frontiers in immunology · 2024Article
- Biomarkers of lymph node metastasis in colorectal cancer: update.Frontiers in oncology · 2024Review
- Targeting intracellular proteins with cell type-specific functions for cancer immunotherapy.Life medicine · 2023Review
- Simultaneously Targeting Two Coupled Signalling Molecules in the Mesenchymal Stem Cell Support Efficiently Sensitises the Multiple Myeloma Cell Line H929 to Bortezomib.International journal of molecular sciences · 2023Article
- Mutual connected IL-6, EGFR and LIN28/Let7-related mechanisms modulate PD-L1 and IGF upregulation in HNSCC using immunotherapy.Frontiers in oncology · 2023Review
- Receptor for activated C kinase 1 promotes cervical cancer lymph node metastasis via the glycolysis‑dependent AKT/mTOR signaling.International journal of oncology · 2022Article
- Anoikis resistance in diffuse glioma: The potential therapeutic targets in the future.Frontiers in oncology · 2022Review
- Rack1 regulates pro-inflammatory cytokines by NF-κB in diabetic nephropathy.Open medicine (Warsaw, Poland) · 2022Article
- Insulin/IGF-1 signaling promotes immunosuppression via the STAT3 pathway: impact on the aging process and age-related diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Review
- Activation of the S100A7/RAGE Pathway by IGF-1 Contributes to Angiogenesis in Breast Cancer.Cancers · 2021Article
- Nrn1 Overexpression Attenuates Retinal Ganglion Cell Apoptosis, Promotes Axonal Regeneration, and Improves Visual Function Following Optic Nerve Crush in Rats.Journal of molecular neuroscience : MN · 2021Article
- Adipocytes: active facilitators in epithelial ovarian cancer progression?Journal of ovarian research · 2020Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Current understanding of the activation of STATs is through binding between the SH2 domain of STATs and phosphotyrosine of tyrosine kinases. Here we demonstrate a novel role of RACK1 as an adaptor for insulin and insulin-like growth factor 1 receptor (IGF-1R)-mediated STAT3 activation specifically. Intracellular association of RACK1 via its N-terminal WD domains 1 to 4 (WD1-4) with insulin receptor (IR)/IGF-1R is augmented upon respective ligand stimulation, whereas association with STAT3 is constitutive. Purified RACK1 or RACK1 WD1-4 associates directly with purified IR, IGF-1R, and STAT3 in vitro. Insulin induces multiprotein complex formation of RACK1, IR, and STAT3. Overexpression or downregulation of RACK1 greatly enhances or decreases, respectively, IR/IGF-1R-mediated activation of STAT3 and its target gene expression. Site-specific mutants of IR and IGF-1R impaired in RACK1 binding are ineffective in mediating recruitment and activation of STAT3 as well as in insulin- or IGF-1-induced protection of cells from anoikis. RACK1-mediated STAT3 activation is important for insulin and IGF-1-induced anchorage-independent growth in certain ovarian cancer cells. We conclude that RACK1 mediates recruitment of STAT3 to IR and IGF-1R specifically for activation, suggesting a general paradigm for the need of an adaptor in mediating activation of STATs by receptor protein tyrosine kinases.
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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.