ArticleMolecular and cellular biology2012
SH2 domain-containing phosphatase 2 is a critical regulator of connective tissue mast cell survival and homeostasis in mice.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- From Stem to Sternum: The Role of Shp2 in the Skeleton.Calcified tissue international · 2023Review
- Therapeutic efficacy of the novel SHP2 degrader SHP2-D26, alone or in combination, against lung cancer is associated with modulation of p70S6K/S6, Bim and Mcl-1.Cancer gene therapy · 2022Article
- KIT as a master regulator of the mast cell lineage.The Journal of allergy and clinical immunology · 2022Review
- PD-1 Regulates Passive Anaphylaxis: A Possible Role of the Mast Cell Intracellular Inhibitory Signal.Allergy, asthma & immunology research · 2021Article
- Mast cells enhance sterile inflammation in chronic nonbacterial osteomyelitis.Disease models & mechanisms · 2019Article
- Shp-2 is critical for ERK and metabolic engagement downstream of IL-15 receptor in NK cells.Nature communications · 2019Article
- SLAP Is a Negative Regulator of FcεRI Receptor-Mediated Signaling and Allergic Response.Frontiers in immunology · 2019Article
- Signal transduction and chemotaxis in mast cells.European journal of pharmacology · 2016Review
- Targeting EPO and EPO receptor pathways in anemia and dysregulated erythropoiesis.Expert opinion on therapeutic targets · 2016Review
- Regulation of Bim in Health and Disease.Oncotarget · 2015Review
- Approaches for analyzing the roles of mast cells and their proteases in vivo.Advances in immunology · 2015Review
- Mast cells and neuroinflammation.Medical science monitor basic research · 2014Review
- Oncogenic KIT-induced aggressive systemic mastocytosis requires SHP2/PTPN11 phosphatase for disease progression in mice.Oncotarget · 2014Article
- SHP2 phosphatase promotes mast cell chemotaxis toward stem cell factor via enhancing activation of the Lyn/Vav/Rac signaling axis.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Phosphatase regulation of immunoreceptor signaling in T cells, B cells and mast cells.Current opinion in immunology · 2013Review
- New models for analyzing mast cell functions in vivo.Trends in immunology · 2012Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Mast cells require KIT receptor tyrosine kinase signaling for development and survival. Here, we report that SH2 domain-containing phosphatase 2 (SHP2) signaling downstream of KIT is essential for mast cell survival and homeostasis in mice. Using a novel mouse model with shp2 deletion within mature mast cells (MC-shp2 knockout [KO]), we find that SHP2 is required for the homeostasis of connective tissue mast cells. Consistently with the loss of skin mast cells, MC-shp2 KO mice fail to mount a passive late-phase cutaneous anaphylaxis response. To better define the phenotype of shp2-deficient mast cells, we used an inducible shp2 knockout approach in bone marrow-derived mast cells (BMMCs) or cultured peritoneal mast cells and found that SHP2 promotes mast cell survival. We show that SHP2 promotes KIT signaling to extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase and downregulation of the proapoptotic protein Bim in BMMCs. Also, SHP2-deficient BMMCs failed to repopulate mast cells in mast cell-deficient mice. Silencing of Bim partially rescued survival defects in shp2-deficient BMMCs, consistent with the importance of a KIT → SHP2 → Ras/ERK pathway in suppressing Bim and promoting mast cell survival. Thus, SHP2 is a key node in a mast cell survival pathway and a new potential therapeutic target in diseases involving mast cells.
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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.