TY - JOUR
T1 - The Phosphatases STS1 and STS2 Regulate Hematopoietic Stem and Progenitor Cell Fitness.
AU - Zhang, Jing
AU - Vakhrusheva, Olesya
AU - Bandi, Srinivasa Rao
AU - Demirel, Özlem
AU - Kazi, Julhash U.
AU - Fernandes, Ramona Gomes
AU - Jakobi, Katja
AU - Eichler, Astrid
AU - Rönnstrand, Lars
AU - Rieger, Michael A
AU - Carpino, Nick
AU - Serve, Hubert
AU - Brandts, Christian H
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
U2 - 10.1016/j.stemcr.2015.08.006
DO - 10.1016/j.stemcr.2015.08.006
M3 - Article
C2 - 26365512
SN - 2213-6711
VL - 5
SP - 633
EP - 646
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 4
ER -