کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10904256 | 1086569 | 2013 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The Src homology 2 protein Shb promotes cell cycle progression in murine hematopoietic stem cells by regulation of focal adhesion kinase activity
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
MPPPAKSCFVEGFRPLCγGMPFAKMEPTCrPDGFRHPCSH2LT-HSCKLSMultipotent progenitorFACSPI3K5-FU5-bromo-2′-deoxyuridine - 5-bromo-2'-deoxyuridineMAPK - MAPKShb - اسبBrdU - بروموداکسی اوریدینProliferation - ترویجhematopoietic stem cells - سلول های بنیادی خونسازHematopoietic progenitor cell - سلول پیش ساز هماتوپوئیتVascular endothelial growth factor - فاکتور رشد اندوتلیال عروقیVascular Endothelial Growth Factor (VEGF) - فاکتور رشد اندوتلیال عروقی (VEGF)Stem Cell Factor - فاکتور سلول بنیادیphosphatidylinositol-3 kinase - فسفاتیدیلینوزیتول 3 کینازphospholipase Cγ - فسفولیپاز Cγfluorescence activated cell sorting - فلورسانس سلول فعال فعال سلول5-fluorouracil - فلوروراسیل-۵، فلوئورواوراسیلmitogen activated kinase - میتوکند فعال کینازp21-activated kinase - کیناز فعال p21focal adhesion kinase - کیناز چسبندگی کانونیT cell receptor - گیرنده سلول Tplatelet-derived growth factor receptor - گیرنده عامل فاکتور رشد یافته پلاکتvascular endothelial growth factor receptor - گیرنده فاکتور رشد اندوتلیال عروقی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The widely expressed adaptor protein Shb has previously been reported to contribute to T cell function due to its association with the T cell receptor and furthermore, several of Shb's known interaction partners are established regulators of blood cell development and function. In addition, Shb deficient embryonic stem cells displayed reduced blood cell colony formation upon differentiation in vitro. The aim of the current study was therefore to explore hematopoietic stem and progenitor cell function in the Shb knockout mouse. Shb deficient bone marrow contained reduced relative numbers of long-term hematopoietic stem cells (LT-HSCs) that exhibited lower proliferation rates. Despite this, Shb knockout LT-HSCs responded promptly by entering the cell cycle in response to genotoxic stress by 5-fluorouracil treatment. In competitive LT-HSC transplantations, Shb null cells initially engrafted as well as the wild-type cells but provided less myeloid expansion over time. Moreover, Shb knockout bone marrow cells exhibited elevated basal activities of focal adhesion kinase/Rac1/p21-activated kinase signaling and reduced responsiveness to Stem Cell Factor stimulation. Consequently, treatment with a focal adhesion kinase inhibitor increased Shb knockout LT-HSC proliferation. The altered signaling characteristics thus provide a plausible mechanistic explanation for the changes in LT-HSC proliferation since these signaling intermediates have all been shown to participate in LT-HSC cell cycle control. In summary, the loss of Shb dependent signaling in bone marrow cells, resulting in elevated focal adhesion kinase activity and reduced proliferative responses in LT-HSCs under steady state hematopoiesis, confers a disadvantage to the maintenance of LT-HSCs over time.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 319, Issue 12, 15 July 2013, Pages 1852-1864
Journal: Experimental Cell Research - Volume 319, Issue 12, 15 July 2013, Pages 1852-1864
نویسندگان
Karin Gustafsson, Garrett Heffner, Pamela L. Wenzel, Matthew Curran, Jan Grawé, Shannon L. McKinney-Freeman, George Q. Daley, Michael Welsh,