TY  - JOUR
AU  - Usenko, Tatiana
AU  - Chan, Gordon
AU  - Torlakovic, Emina
AU  - Klingmüller, Ursula
AU  - Neel, Benjamin G
TI  - Leukemogenic Ptpn11 allele causes defective erythropoiesis in mice.
JO  - PLoS one
VL  - 9
IS  - 10
SN  - 1932-6203
CY  - Lawrence, Kan.
PB  - PLoS
M1  - DKFZ-2017-04478
SP  - e109682 -
PY  - 2014
AB  - Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2), encoded by PTPN11, regulates signaling networks and cell fate in many tissues. Expression of oncogenic PTPN11 in the hematopoietic compartment causes myeloproliferative neoplasm (MPN) in humans and mice. However, the stage-specific effect(s) of mutant Ptpn11 on erythroid development have remained unknown. We found that expression of an activated, leukemogenic Ptpn11 allele, Ptpn11D61Y, specifically in the erythroid lineage causes dyserythropoiesis in mice. Ptpn11D61Y progenitors produce excess cKIT+ CD71+ Ter119- cells and aberrant numbers of cKITl° CD71+ erythroblasts. Mutant erythroblasts show elevated activation of ERK, AKT and STAT3 in response to EPO stimulation, and MEK inhibitor treatment blocks Ptpn11D61Y-evoked erythroid hyperproliferation in vitro. Thus, the expression of oncogenic Ptpn11 causes dyserythropoiesis in a cell-autonomous manner in vivo.
KW  - Antigens, CD (NLM Chemicals)
KW  - Butadienes (NLM Chemicals)
KW  - CD71 antigen (NLM Chemicals)
KW  - Nitriles (NLM Chemicals)
KW  - Protein Kinase Inhibitors (NLM Chemicals)
KW  - Receptors, Transferrin (NLM Chemicals)
KW  - STAT3 Transcription Factor (NLM Chemicals)
KW  - Stat3 protein, mouse (NLM Chemicals)
KW  - U 0126 (NLM Chemicals)
KW  - Erythropoietin (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-kit (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-akt (NLM Chemicals)
KW  - Extracellular Signal-Regulated MAP Kinases (NLM Chemicals)
KW  - Protein Tyrosine Phosphatase, Non-Receptor Type 11 (NLM Chemicals)
KW  - Ptpn11 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25289670
C2  - pmc:PMC4188809
DO  - DOI:10.1371/journal.pone.0109682
UR  - https://inrepo02.dkfz.de/record/128462
ER  -