ArticleBlood2014
Junctional adhesion molecule-A suppresses platelet integrin αIIbβ3 signaling by recruiting Csk to the integrin-c-Src complex.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 66 citations in OpenAlex.
- Homophilic Interactions of Platelet F11R/JAM-A with its Surface-Bound Counterpart Facilitate Thrombus Formation.Thrombosis and haemostasis · 2026Article
- Junctional adhesion molecule-C: A multifunctional mediator of cell adhesion.Cellular and molecular life sciences : CMLS · 2025Review
- JAM-A: Adhesion Receptor and Signaling Regulator in Atherosclerosis.Current atherosclerosis reports · 2025Review
- Csk-mediated Src family kinase regulation dampens neutrophil infiltration during pulmonary infection.JCI insight · 2025Article
- Platelet spreading and clot retraction are regulated by 2 distinct αThe Journal of pharmacology and experimental therapeutics · 2025Article
- Structure, signal transduction, activation, and inhibition of integrin αIIbβ3.Thrombosis journal · 2023Review
- Loss of contact inhibition of locomotion in the absence of JAM-A promotes entotic cell engulfment.iScience · 2022Article
- Homophilic Interaction Between Transmembrane-JAM-A and Soluble JAM-A Regulates Thrombo-Inflammation: Implications for Coronary Artery Disease.JACC. Basic to translational science · 2022Article
- JAM-A interacts with α3β1 integrin and tetraspanins CD151 and CD9 to regulate collective cell migration of polarized epithelial cells.Cellular and molecular life sciences : CMLS · 2022Article
- Junctional Adhesion Molecules: Potential Proteins in Atherosclerosis.Frontiers in cardiovascular medicine · 2022Review
- The F11 Receptor (F11R)/Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A) in cancer progression.Molecular and cellular biochemistry · 2022Review
- Apoptosis signal-regulating kinase 1 regulates immune-mediated thrombocytopenia, thrombosis, and systemic shock.Journal of thrombosis and haemostasis : JTH · 2020Article
- Tetraspanins: integrating cell surface receptors to functional microdomains in homeostasis and disease.Medical microbiology and immunology · 2020Review
- Targeting Opposing Immunological Roles of the Junctional Adhesion Molecule-A in Autoimmunity and Cancer.Frontiers in immunology · 2020Review
- Macrophage-dependent neutrophil recruitment is impaired under conditions of increased intestinal permeability in JAM-A-deficient mice.Mucosal immunology · 2019Article
- Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting.Journal of hematology & oncology · 2019Review
- Role of JAM-A tyrosine phosphorylation in epithelial barrier dysfunction during intestinal inflammation.Molecular biology of the cell · 2019Article
- Junctional adhesion molecule-A: functional diversity through molecular promiscuity.Cellular and molecular life sciences : CMLS · 2018Review
- Review
- Negative regulators of platelet activation and adhesion.Journal of thrombosis and haemostasis : JTH · 2018Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Fibrinogen binding to activated integrin induces outside-in signaling that results in stable platelet aggregates and clot retraction. How integrin αIIbβ3 is discouraged from spontaneous activation is not known. We have recently shown that junctional adhesion molecule-A (JAM-A) renders protection from thrombosis by suppressing integrin outside-in signaling. In this study, we show that JAM-A associates with integrin αIIbβ3 in resting platelets and dissociates upon platelet activation by agonists. We also show that integrin-associated JAM-A is tyrosine phosphorylated and is rapidly dephosphorylated upon platelet activation. C-terminal Src kinase (Csk) binds to tyrosine phosphorylated JAM-A through its Src homology 2 domain. Thus, JAM-A recruits Csk to the integrin-c-Src complex in resting platelets. Csk, in turn, keeps integrin-associated c-Src in an inactive state by phosphorylating Y(529) in its regulatory domain. Absence of JAM-A results in impaired c-SrcY(529) phosphorylation and augmentation of outside-in signaling-dependent c-Src activation. Our results strongly suggest that tyrosine-phosphorylated JAM-A is a Csk-binding protein and functions as an endogenous inhibitor of integrin signaling. JAM-A recruits Csk to the integrin-c-Src complex, where Csk negatively regulates c-Src activation, thereby suppressing the initiation of outside-in signaling. Upon agonist stimulation, JAM-A is dephosphorylated on the tyrosine, allowing the dissociation of Csk from the integrin complex, and thus facilitating outside-in signaling.
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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.