کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1225581 1494802 2013 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Phosphoproteome analyses reveal specific implications of Hcls1, p21-activated kinase 1 and Ezrin in proliferation of a myeloid progenitor cell line downstream of wild-type and ITD mutant Fms-like tyrosine kinase 3 receptors
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Phosphoproteome analyses reveal specific implications of Hcls1, p21-activated kinase 1 and Ezrin in proliferation of a myeloid progenitor cell line downstream of wild-type and ITD mutant Fms-like tyrosine kinase 3 receptors
چکیده انگلیسی

The tyrosine kinase receptor Flt3 (Fms-like tyrosine kinase 3) is almost always expressed in AML (acute myeloid leukemia) cells, and constitutive activation of Flt3 by ITD (internal tandem duplication) mutations is one of the most common molecular alterations known in AML, especially monocytic AML. Furthermore, Flt3-ligand (FL) was shown as an in vitro growth factor for monocytic precursors, pointing to the important role of Flt3 in the regulation of monocyte/macrophage production. To get a relevant model for studying the molecular mechanisms underlying the physiopathological role of Flt3 on monocytic lineage development, we used the IL-3 dependent murine myeloid progenitors FDC-P1 cell line to generate cells stably co-expressing murine Fms (M-CSF receptor) and human Flt3. Wild type (WT)-Flt3 expressing cells could proliferate in an FL-dependent manner, whereas those expressing Flt3-ITD all survived IL-3 deprivation and showed autonomous proliferation, whereas both types of cells could differentiate to monocytic cells in response to M-CSF. Next, by combining phosphoprotein detection or purification, comparative 2D-PAGE and mass spectrometry sequencing, we sought for downstream mediators of Flt3-WT or Flt3-ITD in FD/Fms cell proliferation. Amongst the differentially expressed and/or phosphorylated proteins, 3 showed a specific implication in FD/Fms cell proliferation: Hcls1 and the Pak1/2 in FL-dependent proliferation of Flt3-WT expressing cells and Ezrin in autonomous proliferation of Flt3-ITD expressing cells.

Figure optionsDownload high-quality image (94 K)Download as PowerPoint slideHighlights
► Flt3-ITD induces autonomous proliferation but does not block macrophage differentiation potential in FD/Fms cells.
► Differentially expressed or phosphorylated proteins are induced by Flt3-WT and Flt3-ITD.
► Hcls1 and the Pak1/2 are involved in FL-dependent proliferation of Flt3-WT expressing cells.
► Ezrin is involved in autonomous proliferation of Flt3-ITD expressing cells and increases proliferation signaling by Flt3-WT.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Proteomics - Volume 78, 14 January 2013, Pages 231–244
نویسندگان
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