Abnormal hematopoiesis in Gab2 mutant mice.

Abnormal hematopoiesis in Gab2 mutant mice. Research Abstract Details 

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Abnormal hematopoiesis in Gab2 mutant mice. Abstract Text:

Yi Zhang,Ernesto Diaz-Flores,Geqiang Li,Zhengqi Wang,Zizhen Kang,Eleonora Haviernikova,Sara Rowe,Cheng-Kui Qu,William Tse,Kevin M Shannon,Kevin D Bunting,

Gab2 is an important adapter molecule for cytokine signaling. Despite its major role in signaling by receptors associated with hematopoiesis, the role of Gab2 in hematopoiesis has not been addressed. We report that despite normal numbers of peripheral blood cells, bone marrow cells, and c-Kit(+)Lin(-)Sca-1(+) (KLS) cells, Gab2-deficient hematopoietic cells are deficient in cytokine responsiveness. Significant reductions in the number of colony-forming units in culture (CFU-C) in the presence of limiting cytokine concentrations were observed, and these defects could be completely corrected by retroviral complementation. In earlier hematopoiesis, Gab2-deficient KLS cells isolated in vitro responded poorly to hematopoietic growth factors, resulting in an up to 11-fold reduction in response to a cocktail of stem cell factor, flt3 ligand, and thrombopoietin. Gab2-deficient c-Kit(+)Lin(-) cells also demonstrate impaired activation of extracellular signal-regulated kinase (ERK) and S6 in response to IL-3, which supports defects in activating the phosphatidylinositol-3 kinase (PI-3K) and mitogen-associated protein kinase (MAPK) signaling cascades. Associated with the early defects in cytokine response, competitive transplantation of Gab2(-/-) bone marrow cells resulted in defective long-term multilineage repopulation. Therefore, we demonstrate that Gab2 adapter function is intrinsically required for hematopoietic cell response to early-acting cytokines, resulting in defective hematopoiesis in Gab2-deficient mice.

Abnormal hematopoiesis in Gab2 mutant mice. Publishing Authors By Initials

Y Zhang,E Diaz-Flores,G Li,Z Wang,Z Kang,E Haviernikova,S Rowe,CK Qu,W Tse,KM Shannon,KD Bunting,

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Abnormal hematopoiesis in Gab2 mutant mice. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Blood

VOLUME: 110

Page Numbers: 116-24

Journal Abbreviation: Blood

ISSN: 0006-4971

DAY: 20

MONTH: 03

YEAR: 2007

Abnormal hematopoiesis in Gab2 mutant mice. Information

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LANGUAGE: eng

NlmUniqueID: 7603509

Abnormal hematopoiesis in Gab2 mutant mice. Keywords Mesh Terms:

KEYWORDS: Stem Cells

MESH TERMS: cytology

Chemical & Substance for Abstract: Abnormal hematopoiesis in Gab2 mutant mice. Information

Substance Name: Phosphoproteins

Registry Number: 0

Grant and Affiliation Information for Abnormal hematopoiesis in Gab2 mutant mice.

AFFILIATION: Department of Medicine, Division of Hematology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-7284, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: R01HL073738

ACRONYM: HL

MEDLINETA: Blood

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