ArticleThe Journal of biological chemistry2012
Cross-talk between integrin α6β4 and insulin-like growth factor-1 receptor (IGF1R) through direct α6β4 binding to IGF1 and subsequent α6β4-IGF1-IGF1R ternary complex formation in anchorage-independent conditions.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
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- A Comprehensive Review of Protein Biomarkers for Invasive Lung Cancer.Current oncology (Toronto, Ont.) · 2024Review
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- IGF/mTORC1/S6 Signaling Is Potentiated and Prolonged by Acute Loading of Subtoxicological Manganese Ion.Biomolecules · 2023Article
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- Drugging IGF-1R in cancer: New insights and emerging opportunities.Genes & diseases · 2023Review
- Autoregulation of insulin receptor signaling through MFGE8 and the αvβ5 integrin.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Novel fibrin-fibronectin matrix accelerates mice skin wound healing.Bioactive materials · 2020Article
- Cell-Surface Proteomics Identifies Differences in Signaling and Adhesion Protein Expression between Naive and Primed Human Pluripotent Stem Cells.Stem cell reports · 2020Article
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- Direct binding to integrins and loss of disulfide linkage in interleukin-1β (IL-1β) are involved in the agonistic action of IL-1β.The Journal of biological chemistry · 2017Article
- HGF potentiates extracellular matrix-driven migration of human myoblasts: involvement of matrix metalloproteinases and MAPK/ERK pathway.Skeletal muscle · 2017Article
- Crosstalk between insulin-like growth factor (IGF) receptor and integrins through direct integrin binding to IGF1.Cytokine & growth factor reviews · 2017Review
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- Fibronectin Interaction and Enhancement of Growth Factors: Importance for Wound Healing.Advances in wound care · 2015Review
- Integrin α1-null mice exhibit improved fatty liver when fed a high fat diet despite severe hepatic insulin resistance.The Journal of biological chemistry · 2015Article
- Proinflammatory secreted phospholipase A2 type IIA (sPLA-IIA) induces integrin activation through direct binding to a newly identified binding site (site 2) in integrins αvβ3, α4β1, and α5β1.The Journal of biological chemistry · 2015Article
- Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Integrin αvβ3 plays a role in insulin-like growth factor-1 (IGF1) signaling (integrin-IGF1 receptor (IGF1R) cross-talk). The specifics of the cross-talk are, however, unclear. In a current model, "ligand occupancy" of αvβ3 (i.e. the binding of extracellular matrix proteins) enhances signaling induced by IGF1 binding to IGF1R. We recently reported that IGF1 directly binds to αvβ3 and induces αvβ3-IGF1-IGF1R ternary complex formation. Consistently, the integrin binding-defective IGF1 mutant (R36E/R37E) is defective in inducing ternary complex formation and IGF signaling, but it still binds to IGF1R. Like αvβ3, integrin α6β4 is overexpressed in many cancers and is implicated in cancer progression. Here, we discovered that α6β4 directly bound to IGF1, but not to R36E/R37E. Grafting the β4 sequence WPNSDP (residues 167-172), which corresponds to the specificity loop of β3, to integrin β1 markedly enhanced IGF1 binding to β1, suggesting that the WPNSDP sequence is involved in IGF1 recognition. WT IGF1 induced α6β4-IGF1-IGF1R ternary complex formation, whereas R36E/R37E did not. When cells were attached to matrix, exogenous IGF1 or α6β4 expression had little or no effect on intracellular signaling. When cell-matrix adhesion was reduced (in poly(2-hydroxyethyl methacrylate-coated plates), IGF1 induced intracellular signaling and enhanced cell survival in an α6β4-dependent manner. Also IGF1 enhanced colony formation in soft agar in an α6β4-dependent manner. These results suggest that IGF binding to α6β4 plays a major role in IGF signaling in anchorage-independent conditions, which mimic the in vivo environment, and is a novel therapeutic target.
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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.