ArticleThe Journal of clinical investigation2003
A novel form of integrin dysfunction involving beta1, beta2, and beta3 integrins.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 95 citations in OpenAlex.
- The thymus gland is a target and maintainer of amyotrophic lateral sclerosis pathophysiology.Brain, behavior, & immunity - health · 2026Article
- Structural basis of kindlin-3 in leukocyte adhesion deficiency III.Journal of thrombosis and haemostasis : JTH · 2026Article
- A novel leukocyte adhesion deficiency type III mutation manifests functional importance of the compact FERM domain in kindlin-3.Journal of thrombosis and haemostasis : JTH · 2024Article
- KRIT1-mediated regulation of neutrophil adhesion and motility.The FEBS journal · 2023Article
- Leukocyte adhesion deficiency III - when integrins activation fails.Journal of clinical immunology · 2014Review
- Neutrophil cell surface receptors and their intracellular signal transduction pathways.International immunopharmacology · 2013Review
- Lessons from rare maladies: leukocyte adhesion deficiency syndromes.Current opinion in hematology · 2013Review
- Novel aspects of Kindlin-3 function in humans based on a new case of leukocyte adhesion deficiency III.Journal of thrombosis and haemostasis : JTH · 2012Article
- Leukocyte adhesion deficiency-I variant syndrome (LAD-Iv, LAD-III): molecular characterization of the defect in an index family.American journal of hematology · 2012Article
- The integrin co-activator Kindlin-3 is expressed and functional in a non-hematopoietic cell, the endothelial cell.The Journal of biological chemistry · 2010Article
- Kindlins in FERM adhesion.Blood · 2010Review
- High-throughput screening based identification of small molecule antagonists of integrin CD11b/CD18 ligand binding.Biochemical and biophysical research communications · 2010Article
- Hematopoetic stem cell transplantation in neutrophil disorders: severe congenital neutropenia, leukocyte adhesion deficiency and chronic granulomatous disease.Clinical reviews in allergy & immunology · 2010Review
- Defects in the leukocyte adhesion cascade.Clinical reviews in allergy & immunology · 2010Review
- Kindling the flame of integrin activation and function with kindlins.Current opinion in hematology · 2009Review
- Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation.Nature medicine · 2009Article
- The clinical spectrum of leukocyte adhesion deficiency (LAD) III due to defective CalDAG-GEF1.Journal of clinical immunology · 2009Article
- Transmembrane helices that form two opposite homodimeric interactions: an asparagine scan study of alphaM and beta2 integrins.Protein science : a publication of the Protein Society · 2008Article
- Loss of talin1 in platelets abrogates integrin activation, platelet aggregation, and thrombus formation in vitro and in vivo.The Journal of experimental medicine · 2007Article
- A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets.The Journal of experimental medicine · 2007Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adhesion receptors known as integrins perform key functions for hematopoietic cells. The platelet integrin alphaIIbbeta3 is critical in hemostasis, and the beta1 and beta2 integrins on leukocytes have many roles in cell-mediated immunity. Mutations in the beta2 subunit lead to integrin nonexpression and to an immune deficiency, leukocyte adhesion deficiency-1. Mutations in either the alpha or beta subunit of alphaIIbbeta3 usually lead to integrin nonexpression and a bleeding tendency termed Glanzmann thrombasthenia. Here we describe a unique patient with clinical features of both Glanzmann thrombasthenia and leukocyte adhesion deficiency-1. The patient has normal expression of beta1, beta2, and beta3 integrins, but all are dysfunctional. The key findings are that "inside-out" signaling pathways leading to integrin activation are defective and that this is associated with abnormal integrin clustering. The integrins themselves are intact and capable of function following extracellular stimulation. T cell motility is normal, as are the expression levels and electrophoretic characteristics of all cytoskeletal and signaling proteins tested, except PKC-alpha, which has enhanced expression in the patient's cells. To our knowledge, this is the first description of a dysfunction affecting three classes of integrins. We propose that it is caused by a lesion in an intracellular factor or signaling pathway essential for integrin activation in hematopoietic cells and results in lack of regulation of clustering, an essential component of integrin-mediated adhesion.
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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.