کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1983574 | 1539899 | 2013 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identification and characterization of an alternative splice variant of Mpl with a high affinity for TPO and its activation of ERK1/2 signaling
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کلمات کلیدی
CDKEBPTPOphosphorylated ERK1/2phosphorylated p38MPLCRMRT-PCRmRNA expression levelsp-p38SPFERK1/2 - ERK1 / 2p-ERK1/2 - P-ERK1 / 2p38 MAPK - P38 MAPKThrombopoietin - ترومبوپوتیینDNA binding domain - دامنه اتصال DNAintracellular domain - دامنه درون سلولیtransmembrane domain - دامنه فرابنفشactivation domain - دامنه فعال سازیICD - دفیبریلاتورهای کاردیوورتر کاشتنیActive conformation - سازگاری فعالBinding affinity - وابستگیReverse transcriptase-polymerase chain reaction - واکنش زنجیره ای واکنش زنجیره ای واکنش زنجیره ایp38 mitogen-activated protein kinase - پروتئین کیناز متیوژن فعال p38Signal peptide - پپتید سیگنالcyclin-dependent kinases - کیناز وابسته به سیکلین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The thrombopoietin receptor is a crucial element in thrombopoietin-initiated signaling pathways, which stimulates the differentiation of normal hematopoietic progenitor cells, the maturation of megakaryocytes, and the generation of platelets. In this study, we identified a novel activating variant of thrombopoietin receptor, termed Mpl-D, in human megakaryoblastic leukemia Dami cells and demonstrated that the binding affinity of the Mpl-D receptor for thrombopoietin is enhanced. Cell cycle analysis revealed that in the presence of thrombopoietin, most Mpl-D expressing NIH3T3 (NIH3T3/Mpl-D) cells were prevalent in G1 phase while the S and G2/M populations were less frequently observed. Unexpectedly, thrombopoietin induced strong and prolonged ERK1/2 signaling in NIH3T3/Mpl-D cells compared with its receptor wild-type expressing NIH3T3 (NIH3T3/Mpl-F) cells. Further analysis of the mRNA levels of cyclin D1/D2 in NIH3T3/Mpl-D cells demonstrated markedly down-regulated expression compared to NIH3T3/Mpl-F cells in the presence of thrombopoietin. Thus, the prolonged activation of ERK1/2 by Mpl-D might lead to G1 cell cycle arrest through a profound reduction of cyclin D1/D2 in order to support cell survival without proliferation. We also provided tertiary structural basis for the Mpl-D and thrombopoietin interaction, which might provide insights into how Mpl-D effectively increases binding to thrombopoietin and significantly contributes to its specific signaling pathway. These results suggest a new paradigm for the regulation of cytokine receptor expression and function through the alternative splicing variant of Mpl in Dami cells, which may play a role in the pathogenesis of megakaryoblastic leukemia.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 45, Issue 12, December 2013, Pages 2852-2863
Journal: The International Journal of Biochemistry & Cell Biology - Volume 45, Issue 12, December 2013, Pages 2852-2863
نویسندگان
Qiong Wang, Rui Sun, Leyan Wu, Junfeng Huang, Ping Wang, Hailong Yuan, Feifei Qiu, Xiaohong Xu, Di Wu, Ying Yu, Xin Liu, Qing Zhang,