| First Author | Zhang J | Year | 2015 |
| Journal | Stem Cell Reports | Volume | 5 |
| Issue | 4 | Pages | 633-46 |
| PubMed ID | 26365512 | Mgi Jnum | J:239223 |
| Mgi Id | MGI:5827857 | Doi | 10.1016/j.stemcr.2015.08.006 |
| Citation | Zhang J, et al. (2015) The Phosphatases STS1 and STS2 Regulate Hematopoietic Stem and Progenitor Cell Fitness. Stem Cell Reports 5(4):633-46 |
| abstractText | 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. |
