ArticleThe Journal of biological chemistry2015
Protein-tyrosine phosphatase Shp2 positively regulates macrophage oxidative burst.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Notch-1 in macrophages promoted the ischemia-reperfusion via modulating EZH2/HSF1/BRD4/SIRPα/SHP2 induced ROS and apoptosis in cardiomyocyte.Scientific reports · 2026Article
- SHP2: A Redox-Sensitive Regulator Linking Immune Checkpoint Inhibitor Therapy to Cancer Treatment and Vascular Risk.Antioxidants (Basel, Switzerland) · 2025Review
- Targeting the Dectin-1 Receptor in Neuroinflammation: Therapeutic Implications for Neuropsychiatric Disorders.ACS chemical neuroscience · 2025Review
- Tyrosine phosphatase Shp2 accelerated the progression of dilated cardiomyopathy via upregulating NF-κB/Src/FAK signaling induced ROS and mitophagy.Scientific reports · 2025Article
- SHP2-mediated ROS activation induces chondrocyte paraptosis in osteoarthritis and is attenuated by low-intensity pulsed ultrasound.Journal of orthopaedic translation · 2025Article
- Lysosomes finely control macrophage inflammatory function via regulating the release of lysosomal FeNature communications · 2025Article
- Exploration of the Dual Role of Dectin-1 in Tumor Development and Its Therapeutic Potential.Current oncology (Toronto, Ont.) · 2024Review
- SHP2 regulates adipose maintenance and adipocyte-pancreatic cancer cell crosstalk via PDHA1.Journal of cell communication and signaling · 2023Article
- The Contribution of Oxidative Stress toAntioxidants (Basel, Switzerland) · 2023Review
- Dectin-1 Signaling Update: New Perspectives for Trained Immunity.Frontiers in immunology · 2022Review
- Siglecs as Therapeutic Targets in Cancer.Biology · 2021Review
- Oxidants in Physiological Processes.Handbook of experimental pharmacology · 2021Review
- Development and Characterization of an Endotoxemia Model in Zebra Fish.Frontiers in immunology · 2018Article
- Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer.Antioxidants & redox signaling · 2017Article
- Engineered proteins with sensing and activating modules for automated reprogramming of cellular functions.Nature communications · 2017Article
- Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Restriction of Aerobic Metabolism by Acquired or Innate Arylsulfatase B Deficiency: A New Approach to the Warburg Effect.Scientific reports · 2016Article
- Neurofibromin is a novel regulator of Ras-induced reactive oxygen species production in mice and humans.Free radical biology & medicine · 2016Article
- Keyhole limpet hemocyanin induces innate immunity via Syk and Erk phosphorylation.EXCLI journal · 2016Article
- Genome-Wide Transcriptional Analysis Reveals the Protection against Hypoxia-Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways.Oxidative medicine and cellular longevity · 2016Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
Macrophages are vital to innate immunity and express pattern recognition receptors and integrins for the rapid detection of invading pathogens. Stimulation of Dectin-1 and complement receptor 3 (CR3) activates Erk- and Akt-dependent production of reactive oxygen species (ROS). Shp2, a protein-tyrosine phosphatase encoded by Ptpn11, promotes activation of Ras-Erk and PI3K-Akt and is crucial for hematopoietic cell function; however, no studies have examined Shp2 function in particulate-stimulated ROS production. Maximal Dectin-1-stimulated ROS production corresponded kinetically to maximal Shp2 and Erk phosphorylation. Bone marrow-derived macrophages (BMMs) from mice with a conditionally deleted allele of Ptpn11 (Shp2(flox/flox);Mx1Cre+) produced significantly lower ROS levels compared with control BMMs. Although YFP-tagged phosphatase dead Shp2-C463A was strongly recruited to the early phagosome, its expression inhibited Dectin-1- and CR3-stimulated phospho-Erk and ROS levels, placing Shp2 phosphatase function and Erk activation upstream of ROS production. Further, BMMs expressing gain of function Shp2-D61Y or Shp2-E76K and peritoneal exudate macrophages from Shp2D61Y/+;Mx1Cre+ mice produced significantly elevated levels of Dectin-1- and CR3-stimulated ROS, which was reduced by pharmacologic inhibition of Erk. SIRPα (signal regulatory protein α) is a myeloid inhibitory immunoreceptor that requires tyrosine phosphorylation to exert its inhibitory effect. YFP-Shp2C463A-expressing cells have elevated phospho-SIRPα levels and an increased Shp2-SIRPα interaction compared with YFP-WT Shp2-expressing cells. Collectively, these findings indicate that Shp2 phosphatase function positively regulates Dectin-1- and CR3-stimulated ROS production in macrophages by dephosphorylating and thus mitigating the inhibitory function of SIRPα and by promoting Erk activation.
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Registered trials
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