ArticleBlood2007
Requirement of alpha and beta subunit transmembrane helix separation for integrin outside-in signaling.
Article in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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
70 citing papers in PubMed, 123 citations in OpenAlex.
- Exosome Nanotherapy Rescues Male Fertility by Delivering Integrin β1 to Repair Environmental Stress-Damaged Testes.Molecular pharmaceutics · 2026Article
- MnBiophysical journal · 2025Article
- Allosteric Disulfide Bridges in Integrins: The Molecular Switches of Redox Regulation of Integrin-Mediated Cell Functions.Antioxidants (Basel, Switzerland) · 2025Review
- FERMT2 drives anoikis resistance and peritoneal metastasis by enhancing extracellular matrix deposition in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- LFA-1: A potential key player in microglia-mediated neuroprotection against oxygen-glucose deprivation in vitro.PloS one · 2025Article
- Full-length αIIbβ3 cryo-EM structure reveals intact integrin initiate-activation intrinsic architecture.Structure (London, England : 1993) · 2024Article
- Integrinβ-1 in disorders and cancers: molecular mechanisms and therapeutic targets.Cell communication and signaling : CCS · 2024Review
- The mechanism of ITGB4 in tumor migration and invasion.Frontiers in oncology · 2024Review
- Importance of Fibrosis in the Pathogenesis of Uterine Leiomyoma and the Promising Anti-fibrotic Effects of Dipeptidyl Peptidase-4 and Fibroblast Activation Protein Inhibitors in the Treatment of Uterine Leiomyoma.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Autocrine pro-legumain promotes breast cancer metastasis via binding to integrin αvβ3.Oncogene · 2022Article
- Correlation between Platelet Count and Lung Dysfunction in Multiple Trauma Patients-A Retrospective Cohort Analysis.Journal of clinical medicine · 2022Article
- Emerging therapeutic opportunities for integrin inhibitors.Nature reviews. Drug discovery · 2022Review
- Integrin Regulated Autoimmune Disorders: Understanding the Role of Mechanical Force in Autoimmunity.Frontiers in cell and developmental biology · 2022Review
- Integrin α6-Targeted Molecular Imaging of Central Nervous System Leukemia in Mice.Frontiers in bioengineering and biotechnology · 2022Article
- Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression.International journal of molecular sciences · 2021Review
- A High-Resolution Ternary Model Demonstrates How PEGylated 2D Nanomaterial Stimulates Integrin αAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Insight Into Pathological Integrin αIIbβ3 Activation From Safeguarding The Inactive State.Journal of molecular biology · 2021Article
- Specifications of the variant curation guidelines for ITGA2B/ITGB3: ClinGen Platelet Disorder Variant Curation Panel.Blood advances · 2021Article
- The CD28 Transmembrane Domain Contains an Essential Dimerization Motif.Frontiers in immunology · 2020Article
- Pulmonary Endothelial Mechanical Sensing and Signaling, a Story of Focal Adhesions and Integrins in Ventilator Induced Lung Injury.Frontiers in physiology · 2019Review
10 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
6 authors at 3 institutions in 1 country.
Funding
Abstract
Adhesion to extracellular ligands through integrins regulates cell shape, migration, growth, and survival. How integrins transmit signals in the outside-to-in direction remains unknown. Whereas in resting integrins the alpha and beta subunit transmembrane domains are associated, ligand binding promotes dissociation and separation of these domains. Here we address whether such separation is required for outside-in signaling. By introduction of an intersubunit disulfide bond, we generated mutant integrin alphaIIbbeta3 with blocked transmembrane separation that binds ligand, mediates adhesion, adopts an extended conformation after ligand binding, and forms antibody-induced macroclusters on the cell surface similarly to wild type. However, the mutant integrin exhibits a profound defect in adhesion-induced outside-in signaling as measured by cell spreading, actin stress-fiber and focal adhesion formation, and focal adhesion kinase activation. This defect was rescued by reduction of the disulfide bond. Our results demonstrate that the separation of transmembrane domains is required for integrin outside-in signal transduction.
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.