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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • 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
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Hematologi
Originalspråkengelska
Sidor (från-till)633-646
TidskriftStem Cell Reports
Volym5
Utgivningsnummer4
StatusPublished - 2015
PublikationskategoriForskning
Peer review utfördJa