Open AccessPRL2/PTP4A2 Phosphatase Is Important for Hematopoietic Stem Cell Self‐Renewal
Author(s) -
Kobayashi Michihiro,
Bai Yunpeng,
Dong Yuanshu,
Yu Hao,
Chen Sisi,
Gao Rui,
Zhang Lujuan,
Yoder Mervin C.,
Kapur Reuben,
Zhang ZhongYin,
Liu Yan
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1672
Subject(s) - biology , stem cell , stem cell factor , microbiology and biotechnology , progenitor cell , haematopoiesis , protein kinase b , proto oncogene proteins c kit , protein tyrosine phosphatase , hematopoietic stem cell , signal transduction , mapk/erk pathway , cancer research
Hematopoietic stem cell (HSC) self‐renewal is tightly controlled by cytokines and other signals in the microenvironment. While stem cell factor (SCF) is an early acting cytokine that activates the receptor tyrosine kinase KIT and promotes HSC maintenance, how SCF/KIT signaling is regulated in HSCs is poorly understood. The protein tyrosine phosphatase 4A (PTP4A) family (aka PRL [phosphatase of regenerating liver] phosphatases), consisting of PTP4A1/PRL1, PTP4A2/PRL2, and PTP4A3/PRL3, represents an intriguing group of phosphatases implicated in cell proliferation and tumorigenesis. However, the role of PTP4A in hematopoiesis remains elusive. To define the role of PTP4A in hematopoiesis, we analyzed HSC behavior in Ptp4a2 ( Prl2 ) deficient mice. We found that Ptp4a2 deficiency impairs HSC self‐renewal as revealed by serial bone marrow transplantation assays. Moreover, we observed that Ptp4a2 null hematopoietic stem and progenitor cells (HSPCs) are more quiescent and show reduced activation of the AKT and ERK signaling. Importantly, we discovered that the ability of PTP4A2 to enhance HSPC proliferation and activation of AKT and ERK signaling depends on its phosphatase activity. Furthermore, we found that PTP4A2 is important for SCF‐mediated HSPC proliferation and loss of Ptp4a2 decreased the ability of oncogenic KIT/D814V mutant in promoting hematopoietic progenitor cell proliferation. Thus, PTP4A2 plays critical roles in regulating HSC self‐renewal and mediating SCF/KIT signaling. S tem C ells 2014;32:1956–1967