The Phosphatases STS1 and STS2 Regulate Hematopoietic Stem and Progenitor Cell Fitness.
(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:
https://lup.lub.lu.se/record/8042393
- author
- organization
- publishing date
- 2015
- 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
- pmid:26365512
- 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
- 2016-04-01 15:02:10
- date last changed
- 2022-03-14 17:00:29
@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}}, doi = {{10.1016/j.stemcr.2015.08.006}}, volume = {{5}}, year = {{2015}}, }