Shp2 and Pten have antagonistic roles in myeloproliferation but cooperate to promote erythropoiesis in mammals

Helen He Zhu, Xiaolin Luo, Kaiqing Zhang, Jian Cui, Huifang Zhao, Zhongzhong Ji, Zhicheng Zhou, Jufang Yao, Lifan Zeng, Kaihong Ji, Wei Qiang Gao, Zhong Yin Zhang, Gen Sheng Feng

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)13342-13347
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number43
DOIs
StatePublished - Oct 27 2015

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Keywords

  • Anemia
  • Erythropoiesis
  • Myeloproliferative neoplasm
  • Pten
  • Shp2

ASJC Scopus subject areas

  • General

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