Advanced

The Phosphatases STS1 and STS2 Regulate Hematopoietic Stem and Progenitor Cell Fitness.

Zhang, Jing; Vakhrusheva, Olesya; Bandi, Srinivasa Rao; Demirel, Özlem; Kazi, Julhash U. LU ; Fernandes, Ramona Gomes; Jakobi, Katja; Eichler, Astrid; Rönnstrand, Lars LU and Rieger, Michael A, et al. (2015) In Stem Cell Reports 5(4). p.633-646
Abstract
FLT3 and c-KIT are crucial regulators of hematopoietic stem and progenitor cells. We investigated the role of STS1 and STS2 on FLT3 and c-KIT phosphorylation, activity, and function in normal and stress-induced hematopoiesis. STS1/STS2-deficient mice show a profound expansion of multipotent progenitor and lymphoid primed multipotent progenitor cells with elevated colony-forming capacity. Although long-term hematopoietic stem cells are not increased in numbers, lack of STS1 and STS2 significantly promotes long-term repopulation activity, demonstrating a pivotal role of STS1/STS2 in regulating hematopoietic stem and progenitor cell fitness. Biochemical analysis identified STS1/STS2 as direct phosphatases of FLT3 and c-KIT. Loss of STS1/STS2... (More)
FLT3 and c-KIT are crucial regulators of hematopoietic stem and progenitor cells. We investigated the role of STS1 and STS2 on FLT3 and c-KIT phosphorylation, activity, and function in normal and stress-induced hematopoiesis. STS1/STS2-deficient mice show a profound expansion of multipotent progenitor and lymphoid primed multipotent progenitor cells with elevated colony-forming capacity. Although long-term hematopoietic stem cells are not increased in numbers, lack of STS1 and STS2 significantly promotes long-term repopulation activity, demonstrating a pivotal role of STS1/STS2 in regulating hematopoietic stem and progenitor cell fitness. Biochemical analysis identified STS1/STS2 as direct phosphatases of FLT3 and c-KIT. Loss of STS1/STS2 induces hyperphosphorylation of FLT3, enhances AKT signaling, and confers a strong proliferative advantage. Therefore, our study reveals that STS1 and STS2 may serve as novel pharmaceutical targets to improve hematopoietic recovery after bone marrow transplantation. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Stem Cell Reports
volume
5
issue
4
pages
633 - 646
publisher
Cell Press
external identifiers
  • pmid:26365512
  • wos:000364990900016
  • scopus:84944441375
ISSN
2213-6711
DOI
10.1016/j.stemcr.2015.08.006
language
English
LU publication?
yes
id
2ec460f0-dfd3-48a0-afd2-7a31d57006ca (old id 8042393)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26365512?dopt=Abstract
date added to LUP
2015-10-04 13:33:32
date last changed
2017-11-05 04:17:56
@article{2ec460f0-dfd3-48a0-afd2-7a31d57006ca,
  abstract     = {FLT3 and c-KIT are crucial regulators of hematopoietic stem and progenitor cells. We investigated the role of STS1 and STS2 on FLT3 and c-KIT phosphorylation, activity, and function in normal and stress-induced hematopoiesis. STS1/STS2-deficient mice show a profound expansion of multipotent progenitor and lymphoid primed multipotent progenitor cells with elevated colony-forming capacity. Although long-term hematopoietic stem cells are not increased in numbers, lack of STS1 and STS2 significantly promotes long-term repopulation activity, demonstrating a pivotal role of STS1/STS2 in regulating hematopoietic stem and progenitor cell fitness. Biochemical analysis identified STS1/STS2 as direct phosphatases of FLT3 and c-KIT. Loss of STS1/STS2 induces hyperphosphorylation of FLT3, enhances AKT signaling, and confers a strong proliferative advantage. Therefore, our study reveals that STS1 and STS2 may serve as novel pharmaceutical targets to improve hematopoietic recovery after bone marrow transplantation.},
  author       = {Zhang, Jing and Vakhrusheva, Olesya and Bandi, Srinivasa Rao and Demirel, Özlem and Kazi, Julhash U. and Fernandes, Ramona Gomes and Jakobi, Katja and Eichler, Astrid and Rönnstrand, Lars and Rieger, Michael A and Carpino, Nick and Serve, Hubert and Brandts, Christian H},
  issn         = {2213-6711},
  language     = {eng},
  number       = {4},
  pages        = {633--646},
  publisher    = {Cell Press},
  series       = {Stem Cell Reports},
  title        = {The Phosphatases STS1 and STS2 Regulate Hematopoietic Stem and Progenitor Cell Fitness.},
  url          = {http://dx.doi.org/10.1016/j.stemcr.2015.08.006},
  volume       = {5},
  year         = {2015},
}