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 Chan

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)961-964
Number of pages4
JournalLeukemia Research
Volume35
Issue number7
DOIs
StatePublished - Jul 2011

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Granulocyte-Macrophage Colony-Stimulating Factor
Protein Kinases
Hypersensitivity
Bone Marrow
KSR-1 protein kinase

Keywords

  • GM-CSF hypersensitivity
  • Juvenile myelomonocytic leukemia
  • KSR1
  • PTPN11
  • Shp2

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

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.; Saadatzadeh, Tirajeh; Yin, Fuqin; Yu, Menggang; Yang, Feng Chun; Chan, Rebecca.

In: Leukemia Research, Vol. 35, No. 7, 07.2011, p. 961-964.

Research output: Contribution to journalArticle

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

AU - Chen, Mia

AU - Sitarski, Sarah A.

AU - Saadatzadeh, Tirajeh

AU - Yin, Fuqin

AU - Yu, Menggang

AU - Yang, Feng Chun

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