ArticleThe Journal of cell biology1998
Complementary roles for receptor clustering and conformational change in the adhesive and signaling functions of integrin alphaIIb beta3.
Article in The Journal of cell biology, 1998. 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
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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
70 citing papers in PubMed, 234 citations in OpenAlex.
- A FAK conundrum is solved: activation and organization of focal adhesion kinase at the plasma membrane.The EMBO journal · 2020Article
- The Inflammatory Response After Ischemic Stroke: Targeting βFrontiers in neuroscience · 2019Review
- Integrin αBlood · 2017Review
- Clustering of integrin α5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cells.Molecular biology of the cell · 2017Article
- Directly Activating the Integrin αIIbβ3 Initiates Outside-In Signaling by Causing αIIbβ3 Clustering.The Journal of biological chemistry · 2016Article
- Kindlin-3 Is Essential for the Resting α4β1 Integrin-mediated Firm Cell Adhesion under Shear Flow Conditions.The Journal of biological chemistry · 2016Article
- Cytoskeletal perturbation leads to platelet dysfunction and thrombocytopenia in variant forms of Glanzmann thrombasthenia.Haematologica · 2016Article
- Factors Associated with Nitric Oxide-mediated β2 Integrin Inhibition of Neutrophils.The Journal of biological chemistry · 2015Article
- Targeting integrin and integrin signaling in treating thrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2015Review
- The talin head domain reinforces integrin-mediated adhesion by promoting adhesion complex stability and clustering.PLoS genetics · 2014Article
- Intermolecular transmembrane domain interactions activate integrin αIIbβ3.The Journal of biological chemistry · 2014Article
- Atomic basis for the species-specific inhibition of αV integrins by monoclonal antibody 17E6 is revealed by the crystal structure of αVβ3 ectodomain-17E6 Fab complex.The Journal of biological chemistry · 2014Article
- Article
- Talin and kindlin: the one-two punch in integrin activation.Frontiers of medicine · 2014Review
- The mechanism of kindlin-mediated activation of integrin αIIbβ3.Current biology : CB · 2013Article
- Article
- Cell surface-expressed phosphatidylserine as therapeutic target to enhance phagocytosis of apoptotic cells.Cell death and differentiation · 2013Article
- The platelet fibrinogen receptor: from megakaryocyte to the mortuary.JRSM cardiovascular disease · 2012Review
- G(12/13) signaling pathways substitute for integrin αIIbβ3-signaling for thromboxane generation in platelets.PloS one · 2011Article
- Tests of integrin transmembrane domain homo-oligomerization during integrin ligand binding and signaling.The Journal of biological chemistry · 2011Article
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
3 authors at 1 institution in 2 countries.
Funding
Abstract
Integrin alphaIIb beta3 mediates platelet aggregation and "outside-in" signaling. It is regulated by changes in receptor conformation and affinity and/or by lateral diffusion and receptor clustering. To document the relative contributions of conformation and clustering to alphaIIb beta3 function, alphaIIb was fused at its cytoplasmic tail to one or two FKBP12 repeats (FKBP). These modified alphaIIb subunits were expressed with beta3 in CHO cells, and the heterodimers could be clustered into morphologically detectable oligomers upon addition of AP1510, a membrane-permeable, bivalent FKBP ligand. Integrin clustering by AP1510 caused binding of fibrinogen and a multivalent (but not monovalent) fibrinogen-mimetic antibody. However, ligand binding due to clustering was only 25-50% of that observed when alphaIIb beta3 affinity was increased by an activating antibody or an activating mutation. The effects of integrin clustering and affinity modulation were additive, and clustering promoted irreversible ligand binding. Clustering of alphaIIb beta3 also promoted cell adhesion to fibrinogen or von Willebrand factor, but not as effectively as affinity modulation. However, clustering was sufficient to trigger fibrinogen-independent tyrosine phosphorylation of pp72(Syk) and fibrinogen-dependent phosphorylation of pp125(FAK), even in non-adherent cells. Thus, receptor clustering and affinity modulation play complementary roles in alphaIIb beta3 function. Affinity modulation is the predominant regulator of ligand binding and cell adhesion, but clustering increases these responses further and triggers protein tyrosine phosphorylation, even in the absence of affinity modulation. Both affinity modulation and clustering may be needed for optimal function of alphaIIb beta3 in platelets.
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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.