| Autor: |
Jing Zhang, Olesya Vakhrusheva, Srinivasa Rao Bandi, Özlem Demirel, Julhash U. Kazi, Ramona Gomes Fernandes, Katja Jakobi, Astrid Eichler, Lars Rönnstrand, Michael A. Rieger, Nick Carpino, Hubert Serve, Christian H. Brandts |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Stem Cell Reports, Vol 5, Iss 4, Pp 633-646 (2015) |
| Druh dokumentu: |
article |
| ISSN: |
2213-6711 |
| DOI: |
10.1016/j.stemcr.2015.08.006 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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