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首页> 外文期刊>Leukemia Research: A Forum for Studies on Leukemia and Normal Hemopoiesis >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.
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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.

机译:支架蛋白Ras 1激酶抑制剂(KSR1)的遗传破坏,在表达活化PTPN11突变体D61Y和E76K的造血祖细胞中差异调节GM-CSF刺激的过度增殖。

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摘要

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.
机译:激活的PTPN11突变体可促进Erk的造血祖细胞过度活化和对GM-CSF的超敏性。我们假设Ras 1激酶抑制剂(KSR1)有助于激活PTPN11诱导的GM-CSF超敏反应。从功能和生化方面评估了表达WT Shp2,Shp2E76K或Shp2D61Y的WT和KSR1-/-小鼠的骨髓祖细胞。在表达Shp2D61Y和ShpE76K的细胞中,KSR1活化和与磷酸-Erk的相互作用得到增强。 KSR1的遗传破坏部分标准化了Shp2E76K诱导的GM-CSF过敏,但未能纠正Shp2D61Y诱导的GM-CSF的过敏。总体而言,这些研究表明,表达Shp2E76K的细胞比表达Shp2D61Y的细胞对GM-CSF超敏反应对KSR1的依赖性更大。

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