NDLI: Kit-Shp2-Kit signaling acts to maintain a functional hematopoietic stem and progenitor cell pool

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Kit-Shp2-Kit signaling acts to maintain a functional hematopoietic stem and progenitor cell pool

Content Provider	Scilit
Author	Zhu, Helen He Ji, Kaihong Alderson, Nazilla He, Zhao Li, Shuangwei Liu, Wen Zhang, Dong-Er Li, Linheng Feng, Gen-Sheng
Copyright Year	2011
Description	The stem cell factor (SCF)/Kit system has served as a classic model in deciphering molecular signaling events in the hematopoietic compartment, and Kit expression is a most critical marker for hematopoietic stem cells (HSCs) and progenitors. However, it remains to be elucidated how Kit expression is regulated in HSCs. Herein we report that a cytoplasmic tyrosine phosphatase Shp2, acting downstream of Kit and other RTKs, promotes Kit gene expression, constituting a Kit-Shp2-Kit signaling axis. Inducible ablation of PTPN11/Shp2 resulted in severe cytopenia in BM, spleen, and peripheral blood in mice. Shp2 removal suppressed the functional pool of HSCs/progenitors, and Shp2-deficient HSCs failed to reconstitute lethally irradiated recipients because of defects in homing, self-renewal, and survival. We show that Shp2 regulates coordinately multiple signals involving up-regulation of Kit expression via Gata2. Therefore, this study reveals a critical role of Shp2 in maintenance of a functional HSC/progenitor pool in adult mammals, at least in part through a kinase-phosphatase-kinase cascade.
Related Links	http://www.bloodjournal.org/content/bloodjournal/117/20/5350.full.pdf
Ending Page	5361
Page Count	12
Starting Page	5350
DOI	10.1182/blood-2011-01-333476
Journal	Blood
Issue Number	20
Volume Number	117
Language	English
Publisher	American Society of Hematology
Publisher Date	2011-05-19
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Hematopoietic Functional Gene Expression Shp2 Kinase Kit Pool Stem Survival Adult Journal: Blood (Vol- 131, Issue- 20)
Content Type	Text
Resource Type	Article

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