ArticleThe Journal of cell biology2002
Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton.
Article in The Journal of cell biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers.
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Who cites it
156 citing papers in PubMed.
- Integrins and tetraspanins mediate CD36-actin coupling and regulate CD36 organization and signaling.The Journal of cell biology · 2026Article
- The Src-Family Kinases Hck, Fgr and Lyn Drive Immune Complex-Mediated Glomerulonephritis Through the Syk Tyrosine Kinase.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Temporal phosphoproteomics reveals key regulators of procoagulant COAT platelet generation.Blood vessels, thrombosis & hemostasis · 2026Article
- The small-molecule Syk inhibitor R788 inhibits hematopoiesis and worsens anemia in sickle cell disease mice.Blood vessels, thrombosis & hemostasis · 2026Article
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- STIM1/2 maintain signaling competence at ER-PM contact sites during neutrophil spreading.The Journal of cell biology · 2025Article
- Platelet spreading and clot retraction are regulated by 2 distinct αThe Journal of pharmacology and experimental therapeutics · 2025Article
- Vav family exchange factors: Potential regulator in atherosclerosis.Biochemistry and biophysics reports · 2024Review
- The relative importance of platelet integrins in hemostasis, thrombosis and beyond.Haematologica · 2023Review
- Article
- Functional roles of SRC signaling in pancreatic cancer: Recent insights provide novel therapeutic opportunities.Oncogene · 2023Review
- Structure, signal transduction, activation, and inhibition of integrin αIIbβ3.Thrombosis journal · 2023Review
- CSK-mediated signalling by integrins in cancer.Frontiers in cell and developmental biology · 2023Review
- Clinical Pharmacokinetics and Pharmacodynamics of Fostamatinib and Its Active Moiety R406.Clinical pharmacokinetics · 2022Review
- Targeting the RT loop of Src SH3 in Platelets Prevents Thrombosis without Compromising Hemostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- How integrin phosphorylations regulate cell adhesion and signaling.Trends in biochemical sciences · 2022Review
- Platelet Membrane: An Outstanding Factor in Cancer Metastasis.Membranes · 2022Review
- The binding of autotaxin to integrins mediates hyperhomocysteinemia-potentiated platelet activation and thrombosis in mice and humans.Blood advances · 2022Article
- PD-L1 Regulates Platelet Activation and ThrombosisFrontiers in pharmacology · 2022Article
- Signaling Enzymes and Ion Channels Being Modulated by the Actin Cytoskeleton at the Plasma Membrane.International journal of molecular sciences · 2021Review
96 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Integrins regulate cell adhesion and motility through tyrosine kinases, but initiation of this process is poorly understood. We find here that Src associates constitutively with integrin alphaIIbbeta3 in platelets. Platelet adhesion to fibrinogen caused a rapid increase in alphaIIbbeta3-associated Src activity, and active Src localized to filopodia and cell edges. Csk, which negatively regulates Src by phosphorylating Tyr-529, was also constitutively associated with alphaIIbbeta3. However, fibrinogen binding caused Csk to dissociate from alphaIIbbeta3, concomitant with dephosphorylation of Src Tyr-529 and phosphorylation of Src activation loop Tyr-418. In contrast to the behavior of Src and Csk, Syk was associated with alphaIIbbeta3 only after fibrinogen binding. Platelets multiply deficient in Src, Hck, Fgr, and Lyn, or normal platelets treated with Src kinase inhibitors failed to spread on fibrinogen. Inhibition of Src kinases blocked Syk activation and inhibited phosphorylation of Syk substrates (Vav1, Vav3, SLP-76) implicated in cytoskeletal regulation. Syk-deficient platelets exhibited Src activation upon adhesion to fibrinogen, but no spreading or phosphorylation of Vav1, Vav3, and SLP-76. These studies establish that platelet spreading on fibrinogen requires sequential activation of Src and Syk in proximity to alphaIIbbeta3, thus providing a paradigm for initiation of integrin signaling to the actin cytoskeleton.
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Registered trials
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