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000128462 041__ $$aeng
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000128462 1001_ $$aUsenko, Tatiana$$b0
000128462 245__ $$aLeukemogenic Ptpn11 allele causes defective erythropoiesis in mice.
000128462 260__ $$aLawrence, Kan.$$bPLoS$$c2014
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000128462 520__ $$aSrc 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.
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000128462 650_7 $$2NLM Chemicals$$aAntigens, CD
000128462 650_7 $$2NLM Chemicals$$aButadienes
000128462 650_7 $$2NLM Chemicals$$aCD71 antigen
000128462 650_7 $$2NLM Chemicals$$aNitriles
000128462 650_7 $$2NLM Chemicals$$aProtein Kinase Inhibitors
000128462 650_7 $$2NLM Chemicals$$aReceptors, Transferrin
000128462 650_7 $$2NLM Chemicals$$aSTAT3 Transcription Factor
000128462 650_7 $$2NLM Chemicals$$aStat3 protein, mouse
000128462 650_7 $$2NLM Chemicals$$aU 0126
000128462 650_7 $$011096-26-7$$2NLM Chemicals$$aErythropoietin
000128462 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aProto-Oncogene Proteins c-kit
000128462 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aProto-Oncogene Proteins c-akt
000128462 650_7 $$0EC 2.7.11.24$$2NLM Chemicals$$aExtracellular Signal-Regulated MAP Kinases
000128462 650_7 $$0EC 3.1.3.48$$2NLM Chemicals$$aProtein Tyrosine Phosphatase, Non-Receptor Type 11
000128462 650_7 $$0EC 3.1.3.48$$2NLM Chemicals$$aPtpn11 protein, mouse
000128462 7001_ $$aChan, Gordon$$b1
000128462 7001_ $$aTorlakovic, Emina$$b2
000128462 7001_ $$0P:(DE-He78)860df4ab16c373fb28a815dcd81107a6$$aKlingmüller, Ursula$$b3$$udkfz
000128462 7001_ $$aNeel, Benjamin G$$b4
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