PUBLICATION
Protein tyrosine phosphatase PTPN9 regulates erythroid cell development through STAT3 dephosphorylation in zebrafish
- Authors
- Bu, Y., Su, F., Wang, X., Gao, H., Lei, L., Chang, N., Wu, Q., Hu, K., Zhu, X., Chang, Z., Meng, K., Xiong, J.W.
- ID
- ZDB-PUB-140513-152
- Date
- 2014
- Source
- Journal of Cell Science 127(Pt 12): 2761-70 (Journal)
- Registered Authors
- Xiong, Jing-Wei
- Keywords
- none
- MeSH Terms
-
- Animals
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/enzymology
- Erythroid Cells/enzymology*
- Erythropoiesis
- GATA1 Transcription Factor/metabolism
- Gastrulation
- Gene Expression
- Gene Expression Regulation, Developmental
- Humans
- K562 Cells
- Phosphorylation
- Protein Processing, Post-Translational*
- Protein Tyrosine Phosphatases, Non-Receptor/physiology*
- STAT3 Transcription Factor/metabolism*
- Transcription Factors/metabolism
- Zebrafish/embryology
- Zebrafish/physiology*
- Zebrafish Proteins/metabolism*
- Zebrafish Proteins/physiology*
- PubMed
- 24727614 Full text @ J. Cell Sci.
Citation
Bu, Y., Su, F., Wang, X., Gao, H., Lei, L., Chang, N., Wu, Q., Hu, K., Zhu, X., Chang, Z., Meng, K., Xiong, J.W. (2014) Protein tyrosine phosphatase PTPN9 regulates erythroid cell development through STAT3 dephosphorylation in zebrafish. Journal of Cell Science. 127(Pt 12):2761-70.
Abstract
Protein tyrosine phosphatases (PTPs) such as SHP-1, SHP-2 and CD45 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 depleted erythrocytes by inhibiting erythroid cell maturation without affecting erythroid proliferation and apoptosis. Consistently, both dominant-negative PTPN9C515S and PTPN9 siRNA inhibited erythroid differentiation in human K562 cells. Mechanistically, depletion of PTPN9 in zebrafish embryos in vivo or K562 cells in vitro increased phosphorylated STAT3 (pSTAT3), and the hyper-phosphorylated STAT3 entrapped and prevented GATA1 and ZBP-89 from regulating erythroid gene expression. These findings imply that PTPN9 plays an important role in erythropoiesis by disrupting an inhibitory complex of pSTAT3, GATA1 and ZBP-89, providing new cellular and molecular insights of ptpn9a into developmental hematopoiesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping