Essential role for Ptpn11 in survival of hematopoietic stem and progenitor cells

Gordon Chan, Laurene S. Cheung, Wentian Yang, Michael Milyavsky, Ashley D. Sanders, Shengqing Gu, Wan Xing Hong, Aurora X. Liu, Xiaonan Wang, Mary Barbara, Tarun Sharma, Joehleen Gavin, Jeffery L. Kutok, Norman N. Iscove, Kevin M. Shannon, John E. Dick, Benjamin G. Neel, Benjamin S. Braun

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

תקציר

Src homology 2 domain-containing phosphatase 2 (Shp2), encoded by Ptpn11, is a member of the nonreceptor proteintyrosine phosphatase family, and functions in cell survival, proliferation, migration, and differentiation in many tissues. Here we report that loss of Ptpn11 in murine hematopoietic cells leads to bone marrow aplasia and lethality. Mutant mice show rapid loss of hematopoietic stem cells (HSCs) and immature progenitors of all hematopoietic lineages in a gene dosage-dependent and cell-autonomous manner. Ptpn11-deficient HSCs and progenitors undergo apoptosis concomitant with increased Noxa expression. Mutant HSCs/progenitors also show defective Erk and Akt activation in response to stem cell factor and diminished thrombopoietin-evoked Erk activation. Activated Kras alleviates the Ptpn11 requirement for colony formation by progenitors and cytokine/growth factor responsiveness of HSCs, indicating that Ras is functionally downstream of Shp2 in these cells. Thus, Shp2 plays a critical role in controlling the survival and maintenance of HSCs and immature progenitors in vivo.

שפה מקוריתאנגלית
עמודים (מ-עד)4253-4261
מספר עמודים9
כתב עתBlood
כרך117
מספר גיליון16
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 21 אפר׳ 2011
פורסם באופן חיצוניכן

ASJC Scopus subject areas

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  • ???subjectarea.asjc.2400.2403???
  • ???subjectarea.asjc.2700.2720???
  • ???subjectarea.asjc.1300.1307???

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