ArticleThe Journal of biological chemistry2013
Tyrosine phosphorylation on spleen tyrosine kinase (Syk) is differentially regulated in human and murine platelets by protein kinase C isoforms.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- A new 3-arylbenzofuran derivative EIE-2 reestablishes Treg-dependent tolerance in rheumatoid arthritis by targeting on Syk induced mTOR and PKCθ imbalance.Frontiers in immunology · 2025Article
- Suppressed ORAI1-STIM1-dependent CaThe Journal of biological chemistry · 2024Article
- Phosphorylation of (Ser 291) in the linker insert of Syk negatively regulates ITAM signaling in platelets.Platelets · 2024Article
- Differential Regulation of GPVI-Induced Btk and Syk Activation by PKC, PKA and PP2A in Human Platelets.International journal of molecular sciences · 2023Article
- mTOR regulates GPVI-mediated platelet activation.Journal of translational medicine · 2021Article
- Interspecies differences in protein expression do not impact the spatiotemporal regulation of glycoprotein VI mediated activation.Journal of thrombosis and haemostasis : JTH · 2020Article
- Feedback Regulation of Syk by Protein Kinase C in Human Platelets.International journal of molecular sciences · 2019Article
- cAMP- and cGMP-elevating agents inhibit GPIbα-mediated aggregation but not GPIbα-stimulated Syk activation in human platelets.Cell communication and signaling : CCS · 2019Article
- Amurensin H, a Derivative From Resveratrol, Ameliorates Lipopolysaccharide/Cigarette Smoke-Induced Airway Inflammation by Blocking the Syk/NF-κB Pathway.Frontiers in pharmacology · 2019Article
- Possible Molecular Targets of Novel Ruthenium Complexes in Antiplatelet Therapy.International journal of molecular sciences · 2018Review
- SP6616 as a new Kv2.1 channel inhibitor efficiently promotes β-cell survival involving both PKC/Erk1/2 and CaM/PI3K/Akt signaling pathways.Cell death & disease · 2016Article
- Anti-miR-148a regulates platelet FcγRIIA signaling and decreases thrombosis in vivo in mice.Blood · 2015Article
- Modulation of gastric mucosal inflammatory responses to Helicobacter pylori via ghrelin-induced protein kinase Cδ tyrosine phosphorylation.Inflammopharmacology · 2014Article
- Intracellular Ca2+ oscillations generated via the Ca2+-sensing receptor are mediated by negative feedback by PKCα at Thr888.American journal of physiology. Cell physiology · 2014Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Protein kinase C (PKC) isoforms differentially regulate platelet functional responses downstream of glycoprotein VI (GPVI) signaling, but the role of PKCs regulating upstream effectors such as Syk is not known. We investigated the role of PKC on Syk tyrosine phosphorylation using the pan-PKC inhibitor GF109203X (GFX). GPVI-mediated phosphorylation on Syk Tyr-323, Tyr-352, and Tyr-525/526 was rapidly dephosphorylated, but GFX treatment inhibited this dephosphorylation on Tyr-525/526 in human platelets but not in wild type murine platelets. GFX treatment did not affect tyrosine phosphorylation on FcRγ chain or Src family kinases. Phosphorylation of Lat Tyr-191 and PLCγ2 Tyr-759 was also increased upon treatment with GFX. We evaluated whether secreted ADP is required for such dephosphorylation. Exogenous addition of ADP to GFX-treated platelets did not affect tyrosine phosphorylation on Syk. FcγRIIA- or CLEC-2-mediated Syk tyrosine phosphorylation was also potentiated with GFX in human platelets. Because potentiation of Syk phosphorylation is not observed in murine platelets, PKC-deficient mice cannot be used to identify the PKC isoform regulating Syk phosphorylation. We therefore used selective inhibitors of PKC isoforms. Only PKCβ inhibition resulted in Syk hyperphosphorylation similar to that in platelets treated with GFX. This result indicates that PKCβ is the isoform responsible for Syk negative regulation in human platelets. In conclusion, we have elucidated a novel pathway of Syk regulation by PKCβ in human platelets.
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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.