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

Summary, in English

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.

• 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
• Avdelning/ar: Avdelningen för translationell cancerforskning; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publiceringsår: 2015
• Språk: Engelska
• Sidor: 633-646
• Publikation/Tidskrift/Serie: Stem Cell Reports
• Volym: 5
• Issue: 4
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/26365512?dopt=Abstract; http://dx.doi.org/10.1016/j.stemcr.2015.08.006
• Dokumenttyp: Artikel i tidskrift
• Förlag: Cell Press
• Ämne: Hematology
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 2213-6711