ArticleThe EMBO journal1997
Regulation of the pp72syk protein tyrosine kinase by platelet integrin alpha IIb beta 3.
Article in The EMBO journal, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 168 citations in OpenAlex.
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Shear and Integrin Outside-In Signaling Activate NADPH-Oxidase 2 to Promote Platelet Activation.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Identification of Inhibitors of Integrin Cytoplasmic Domain Interactions With Syk.Frontiers in immunology · 2020Article
- Role of Platelet Glycoprotein VI and Tyrosine Kinase Syk in Thrombus Formation on Collagen-Like Surfaces.International journal of molecular sciences · 2019Article
- Human Platelet Protein Ubiquitylation and Changes following GPVI Activation.Thrombosis and haemostasis · 2019Article
- Platelet collagen receptor Glycoprotein VI-dimer recognizes fibrinogen and fibrin through their D-domains, contributing to platelet adhesion and activation during thrombus formation.Journal of thrombosis and haemostasis : JTH · 2018Article
- Integrin αBlood · 2017Review
- Central role of PI3K-SYK interaction in fibrinogen-induced lamellipodia and filopodia formation in platelets.FEBS open bio · 2016Article
- Directly Activating the Integrin αIIbβ3 Initiates Outside-In Signaling by Causing αIIbβ3 Clustering.The Journal of biological chemistry · 2016Article
- Dok-1 negatively regulates platelet integrin αIIbβ3 outside-in signalling and inhibits thrombosis in mice.Thrombosis and haemostasis · 2016Article
- The N-terminal SH2 domain of Syk is required for (hem)ITAM, but not integrin, signaling in mouse platelets.Blood · 2015Article
- The β isoform of the catalytic subunit of protein phosphatase 2B restrains platelet function by suppressing outside-in αII b β3 integrin signaling.Journal of thrombosis and haemostasis : JTH · 2014Article
- Platelet mechanosensing of substrate stiffness during clot formation mediates adhesion, spreading, and activation.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Depletion of STAT5 blocks TEL-SYK-induced APMF-type leukemia with myelofibrosis and myelodysplasia in mice.Blood cancer journal · 2014Article
- Differential Cav2.1 and Cav2.3 channel inhibition by baclofen and α-conotoxin Vc1.1 via GABAB receptor activation.The Journal of general physiology · 2014Article
- Cooperative integrin/ITAM signaling in platelets enhances thrombus formation in vitro and in vivo.Blood · 2013Article
- Peptide LSARLAF induces integrin β3 dependent outside-in signaling in platelets.Thrombosis research · 2012Article
- The SYK tyrosine kinase: a crucial player in diverse biological functions.Nature reviews. Immunology · 2010Review
- Role of the protein tyrosine kinase Syk in regulating cell-cell adhesion and motility in breast cancer cells.Molecular cancer research : MCR · 2009Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
pp72syk is essential for development and function of several hematopoietic cells, and it becomes activated through tandem SH2 interaction with ITAM motifs in immune response receptors. Since Syk is also activated through integrins, which do not contain ITAMs, a CHO cell model system was used to study Syk activation by the platelet integrin, alpha IIb beta 3. As in platelets, Syk underwent tyrosine phosphorylation and activation during CHO cell adhesion to alpha IIb beta 3 ligands, including fibrinogen. This involved Syk autophosphorylation and the tyrosine kinase activity of Src, and it exhibited two novel features. Firstly, unlike alpha IIb beta 3-mediated activation of pp125FAK, Syk activation could be triggered by the binding of soluble fibrinogen and abolished by truncation of the alpha IIb or beta 3 cytoplasmic tail, and it was resistant to inhibition by cytochalasin D. Secondly, it did not require phosphorylated ITAMs since it was unaffected by disruption of an ITAM-interaction motif in the SH2(C) domain of Syk or by simultaneous overexpression of the tandem SH2 domains. These studies demonstrate that Syk is a proximal component in alpha IIb beta 3 signaling and is regulated as a consequence of intimate functional relationships with the alpha IIb beta 3 cytoplasmic tails and with Src or a closely related kinase. Furthermore, there are fundamental differences in the activation of Syk by alpha IIb beta 3 and immune response receptors, suggesting a unique role for integrins in Syk function.
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