| RRC ID |
33645
|
| 著者 |
Bu Y, Su F, Wang X, Gao H, Lei L, Chang N, Wu Q, Hu K, Zhu X, Chang Z, Meng K, Xiong JW.
|
| タイトル |
Protein tyrosine phosphatase PTPN9 regulates erythroid cell development through STAT3 dephosphorylation in zebrafish.
|
| ジャーナル |
J Cell Sci
|
| 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.
|
| 巻・号 |
127(Pt 12)
|
| ページ |
2761-70
|
| 公開日 |
2014-6-15
|
| DOI |
10.1242/jcs.145367
|
| PII |
jcs.145367
|
| PMID |
24727614
|
| MeSH |
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*
|
| IF |
4.573
|
| 引用数 |
8
|
|
WOS 分野
|
CELL BIOLOGY
|
| リソース情報 |
| ゼブラフィッシュ |
Tg(EF1α:mAG-zGem(1/100))/rw0410h |
