ArticleBlood2011
A critical role for SHP2 in STAT5 activation and growth factor-mediated proliferation, survival, and differentiation of human CD34+ cells.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Allosteric SHP2 inhibition increases apoptotic dependency on BCL2 and synergizes with venetoclax in FLT3- and KIT-mutant AML.Cell reports. Medicine · 2023Article
- From Stem to Sternum: The Role of Shp2 in the Skeleton.Calcified tissue international · 2023Review
- The Non-Receptor Protein Tyrosine Phosphatase PTPN6 Mediates a Positive Regulatory Approach From the Interferon Regulatory Factor to the JAK/STAT Pathway inFrontiers in immunology · 2022Article
- Management of Acute Myeloid Leukemia: Current Treatment Options and Future Perspectives.Cancers · 2021Review
- Strategy for Leukemia Treatment Targeting SHP-1,2 and SHIP.Frontiers in cell and developmental biology · 2021Review
- Loss of Shp2 Rescues BDNF/TrkB Signaling and Contributes to Improved Retinal Ganglion Cell Neuroprotection.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Protein Tyrosine Phosphatases as Potential Regulators of STAT3 Signaling.International journal of molecular sciences · 2018Review
- SHP2-Mediated Signal Networks in Stem Cell Homeostasis and Dysfunction.Stem cells international · 2018Review
- Role of SHP2 in hematopoiesis and leukemogenesis.Current opinion in hematology · 2017Review
- Analogous mechanism regulating formation of neocortical basal radial glia and cerebellar Bergmann glia.eLife · 2017Article
- Granulocyte colony-stimulating factor receptor signaling in severe congenital neutropenia, chronic neutrophilic leukemia, and related malignancies.Experimental hematology · 2017Review
- Eosinophil differentiation in the bone marrow is promoted by protein tyrosine phosphatase SHP2.Cell death & disease · 2016Article
- Antigen receptor-mediated depletion of FOXP3 in induced regulatory T-lymphocytes via PTPN2 and FOXO1.Nature communications · 2015Article
- Shp-2 contributes to anti-RSV activity in human pulmonary alveolar epithelial cells by interfering with the IFN-α-induced Jak/Stat1 pathway.Journal of cellular and molecular medicine · 2015Article
- Functions of Shp2 in cancer.Journal of cellular and molecular medicine · 2015Review
- Mutated Ptpn11 alters leukemic stem cell frequency and reduces the sensitivity of acute myeloid leukemia cells to Mcl1 inhibition.Leukemia · 2015Article
- Protein tyrosine phosphatases as wardens of STAT signaling.JAK-STAT · 2014Review
- PTK2 and PTPN11 expression in myelodysplastic syndromes.Clinics (Sao Paulo, Brazil) · 2013Article
- Dissection of the BCR-ABL signaling network using highly specific monobody inhibitors to the SHP2 SH2 domains.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- A comprehensive analysis of GATA-1-regulated miRNAs reveals miR-23a to be a positive modulator of erythropoiesis.Nucleic acids research · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
SHP2, a cytoplasmic protein-tyrosine phosphatase encoded by the PTPN11 gene, plays a critical role in developmental hematopoiesis in the mouse, and gain-of-function mutations of SHP2 are associated with hematopoietic malignancies. However, the role of SHP2 in adult hematopoiesis has not been addressed in previous studies. In addition, the role of SHP2 in human hematopoiesis has not been described. These questions are of considerable importance given the interest in development of SHP2 inhibitors for cancer treatment. We used shRNA-mediated inhibition of SHP2 expression to investigate the function of SHP2 in growth factor (GF) signaling in normal human CD34(+) cells. SHP2 knockdown resulted in markedly reduced proliferation and survival of cells cultured with GF, and reduced colony-forming cell growth. Cells expressing gain-of-function SHP2 mutations demonstrated increased dependency on SHP2 expression for survival compared with cells expressing wild-type SHP2. SHP2 knockdown was associated with significantly reduced myeloid and erythroid differentiation with retention of CD34(+) progenitors with enhanced proliferative capacity. Inhibition of SHP2 expression initially enhanced and later inhibited STAT5 phosphorylation and reduced expression of the antiapoptotic genes MCL1 and BCLXL. These results indicate an important role for SHP2 in STAT5 activation and GF-mediated proliferation, survival, and differentiation of human progenitor 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.