title: Protein tyrosine phosphatase PTPN9 regulates erythroid cell development through STAT3 dephosphorylation in zebrafish.
abstract: Protein tyrosine phosphatases (PTPs) are involved in hematopoiesis, but the function of many PTPs is not well characterized in vivo. Here, we have identified Ptpn9a, an ortholog of human PTPN9, as a crucial regulator of erythroid cell development in zebrafish embryos. ptpn9a, but not ptpn9b, was expressed in the posterior lateral plate mesoderm and intermediate cell mass - two primitive hematopoietic sites during zebrafish embryogenesis. Morpholino-mediated knockdown of ptpn9a caused erythrocytes to be depleted by inhibiting erythroid cell maturation without affecting erythroid proliferation and apoptosis. Consistently, both dominant-negative PTPN9 (with mutation C515S) and siRNA against PTPN9 inhibited erythroid differentiation in human K562 cells. Mechanistically, depletion of ptpn9 in zebrafish embryos in vivo or in K562 cells in vitro increased phosphorylated STAT3, and the hyper-phosphorylated STAT3 entrapped and prevented the transcription factors GATA1 and ZBP-89 (also known as ZNF148) from regulating erythroid gene expression. These findings imply that PTPN9 plays an important role in erythropoiesis by disrupting an inhibitory complex of phosphorylated STAT3, GATA1 and ZBP-89, providing new cellular and molecular insights into the role of ptpn9a in developmental hematopoiesis.
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, 100871 China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Bu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing, 100084 China.
authors.forename: Fuqin
authors.initials: F
authors.lastname: Su
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, 100871 China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, 100871 China Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing, 100094 China.
authors.forename: Hai
authors.initials: H
authors.lastname: Gao
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, 100871 China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, 100871 China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Chang
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, 100871 China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing, 100094 China.
authors.forename: Keping
authors.initials: K
authors.lastname: Hu
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, 100871 China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing, 100084 China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Chang
authors.affiliation: Beijing Shenogen Biomedical Company Ltd, Beijing, 100085 China kun.meng@shenogen.com jingwei_xiong@pku.edu.cn.
authors.forename: Kun
authors.initials: K
authors.lastname: Meng
authors.affiliation: Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Peking University, Beijing, 100871 China kun.meng@shenogen.com jingwei_xiong@pku.edu.cn.
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Xiong
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000201:enzymology; D041905:Erythroid Cells / Q000201:enzymology*; D004920:Erythropoiesis; D050982:GATA1 Transcription Factor / Q000378:metabolism; D054262:Gastrulation; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D020014:K562 Cells; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism* / Q000502:physiology*
chemical_list: D050982:GATA1 Transcription Factor; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; D029961:Zebrafish Proteins; C494691:gata1a protein, zebrafish; C494089:stat3 protein, zebrafish; C528125:znf148 protein, zebrafish; C000594830:PTPN9a protein, zebrafish; D054558:Protein Tyrosine Phosphatases, Non-Receptor
keywords: Erythroid cell development; K562 cell; PTPN9; STAT3