Genetic disruption of the scaffolding protein, Kinase Suppressor of Ras 1 (KSR1), differentially regulates GM-CSF-stimulated hyperproliferation in hematopoietic progenitors expressing activating PTPN11 mutants D61Y and E76K

Zhenyun Yang; Mia Chen; Sarah A. Sitarski; Tirajeh Saadatzadeh; Fuqin Yin; Menggang Yu; Feng Chun Yang; Rebecca J. Chan

doi:10.1016/j.leukres.2011.04.003

Genetic disruption of the scaffolding protein, Kinase Suppressor of Ras 1 (KSR1), differentially regulates GM-CSF-stimulated hyperproliferation in hematopoietic progenitors expressing activating PTPN11 mutants D61Y and E76K

Zhenyun Yang, Mia Chen, Sarah A. Sitarski, Tirajeh Saadatzadeh, Fuqin Yin, Menggang Yu, Feng Chun Yang, Rebecca J. Chan

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Activating PTPN11 mutants promote hematopoietic progenitor hyperactivation of Erk and hypersensitivity to GM-CSF. We hypothesized that Kinase Suppressor of Ras 1 (KSR1) contributes to activating PTPN11-induced GM-CSF hypersensitivity. Bone marrow progenitors from WT and KSR1-/- mice expressing WT Shp2, Shp2E76K, or Shp2D61Y were evaluated functionally and biochemically. KSR1 activation and interaction with phospho-Erk was enhanced in Shp2D61Y- and ShpE76K-expressing cells. Genetic disruption of KSR1 partially normalized Shp2E76K-induced GM-CSF hypersensitivity, but failed to correct Shp2D61Y-induced GM-CSF hypersensitivity. Collectively, these studies suggest that cells expressing Shp2E76K have a greater dependence on KSR1 for GM-CSF hypersensitivity than cells expressing Shp2D61Y.

Original language	English (US)
Pages (from-to)	961-964
Number of pages	4
Journal	Leukemia Research
Volume	35
Issue number	7
DOIs	https://doi.org/10.1016/j.leukres.2011.04.003
State	Published - Jul 2011
Externally published	Yes

Keywords

GM-CSF hypersensitivity
Juvenile myelomonocytic leukemia
KSR1
PTPN11
Shp2

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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Yang, Z., Chen, M., Sitarski, S. A., Saadatzadeh, T., Yin, F., Yu, M., Yang, F. C., & Chan, R. J. (2011). Genetic disruption of the scaffolding protein, Kinase Suppressor of Ras 1 (KSR1), differentially regulates GM-CSF-stimulated hyperproliferation in hematopoietic progenitors expressing activating PTPN11 mutants D61Y and E76K. Leukemia Research, 35(7), 961-964. https://doi.org/10.1016/j.leukres.2011.04.003

Genetic disruption of the scaffolding protein, Kinase Suppressor of Ras 1 (KSR1), differentially regulates GM-CSF-stimulated hyperproliferation in hematopoietic progenitors expressing activating PTPN11 mutants D61Y and E76K. / Yang, Zhenyun; Chen, Mia; Sitarski, Sarah A. et al.
In: Leukemia Research, Vol. 35, No. 7, 07.2011, p. 961-964.

Research output: Contribution to journal › Article › peer-review

Yang, Z, Chen, M, Sitarski, SA, Saadatzadeh, T, Yin, F, Yu, M, Yang, FC & Chan, RJ 2011, 'Genetic disruption of the scaffolding protein, Kinase Suppressor of Ras 1 (KSR1), differentially regulates GM-CSF-stimulated hyperproliferation in hematopoietic progenitors expressing activating PTPN11 mutants D61Y and E76K', Leukemia Research, vol. 35, no. 7, pp. 961-964. https://doi.org/10.1016/j.leukres.2011.04.003

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title = "Genetic disruption of the scaffolding protein, Kinase Suppressor of Ras 1 (KSR1), differentially regulates GM-CSF-stimulated hyperproliferation in hematopoietic progenitors expressing activating PTPN11 mutants D61Y and E76K",

abstract = "Activating PTPN11 mutants promote hematopoietic progenitor hyperactivation of Erk and hypersensitivity to GM-CSF. We hypothesized that Kinase Suppressor of Ras 1 (KSR1) contributes to activating PTPN11-induced GM-CSF hypersensitivity. Bone marrow progenitors from WT and KSR1-/- mice expressing WT Shp2, Shp2E76K, or Shp2D61Y were evaluated functionally and biochemically. KSR1 activation and interaction with phospho-Erk was enhanced in Shp2D61Y- and ShpE76K-expressing cells. Genetic disruption of KSR1 partially normalized Shp2E76K-induced GM-CSF hypersensitivity, but failed to correct Shp2D61Y-induced GM-CSF hypersensitivity. Collectively, these studies suggest that cells expressing Shp2E76K have a greater dependence on KSR1 for GM-CSF hypersensitivity than cells expressing Shp2D61Y.",

keywords = "GM-CSF hypersensitivity, Juvenile myelomonocytic leukemia, KSR1, PTPN11, Shp2",

author = "Zhenyun Yang and Mia Chen and Sitarski, {Sarah A.} and Tirajeh Saadatzadeh and Fuqin Yin and Menggang Yu and Yang, {Feng Chun} and Chan, {Rebecca J.}",

note = "Funding Information: This work was supported by the U.S. National Institutes of Health (HL082981, RJC) and the U.S. Department of Defense (DOD W81XWH-05-1-0161 and DOD W81XWH-08-1-0071, FCY). The authors gratefully acknowledge the administrative assistance of Linda S. Henson.",

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AU - Chan, Rebecca J.

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Genetic disruption of the scaffolding protein, Kinase Suppressor of Ras 1 (KSR1), differentially regulates GM-CSF-stimulated hyperproliferation in hematopoietic progenitors expressing activating PTPN11 mutants D61Y and E76K

Abstract

Keywords

ASJC Scopus subject areas

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