ArticleProceedings of the National Academy of Sciences of the United States of America2015
Shp2 and Pten have antagonistic roles in myeloproliferation but cooperate to promote erythropoiesis in mammals.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Complex Roles ofAnnual review of cancer biology · 2024Article
- Concurrent Disruption of the Ras/MAPK and NF-κB Pathways Induces Circadian Deregulation and Hepatocarcinogenesis.Molecular cancer research : MCR · 2022Article
- Molecular pathogenesis of the myeloproliferative neoplasms.Journal of hematology & oncology · 2021Review
- Phospho-PTM proteomic discovery of novel EPO- modulated kinases and phosphatases, including PTPN18 as a positive regulator of EPOR/JAK2 Signaling.Cellular signalling · 2020Article
- Tumor immunology and immunotherapy: a journey I started from Hangzhou.Journal of Zhejiang University. Science. B · 2019Article
- The functions and regulation of the PTEN tumour suppressor: new modes and prospects.Nature reviews. Molecular cell biology · 2018Review
- Shp2 deletion in hepatocytes suppresses hepatocarcinogenesis driven by oncogenic β-Catenin, PIK3CA and MET.Journal of hepatology · 2018Article
- β-catenin deficiency in hepatocytes aggravates hepatocarcinogenesis driven by oncogenic β-catenin and MET.Hepatology (Baltimore, Md.) · 2018Article
- Role of SHP2 in hematopoiesis and leukemogenesis.Current opinion in hematology · 2017Review
- Dual Shp2 and Pten Deficiencies Promote Non-alcoholic Steatohepatitis and Genesis of Liver Tumor-Initiating Cells.Cell reports · 2016Article
- Treating leukemia at the risk of inducing severe anemia.Experimental hematology · 2016Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Previous data suggested a negative role of phosphatase and tensin homolog (Pten) and a positive function of SH2-containing tyrosine phosphatase (Shp2)/Ptpn11 in myelopoiesis and leukemogenesis. Herein we demonstrate that ablating Shp2 indeed suppressed the myeloproliferative effect of Pten loss, indicating directly opposing functions between pathways regulated by these two enzymes. Surprisingly, the Shp2 and Pten double-knockout mice suffered lethal anemia, a phenotype that reveals previously unappreciated cooperative roles of Pten and Shp2 in erythropoiesis. The lethal anemia was caused collectively by skewed progenitor differentiation and shortened erythrocyte lifespan. Consistently, treatment of Pten-deficient mice with a specific Shp2 inhibitor suppressed myeloproliferative neoplasm while causing anemia. These results identify concerted actions of Pten and Shp2 in promoting erythropoiesis, while acting antagonistically in myeloproliferative neoplasm development. This study illustrates cell type-specific signal cross-talk in blood cell lineages, and will guide better design of pharmaceuticals for leukemia and other types of cancer in the era of precision medicine.
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