کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10768057 1050803 2005 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Calmodulin physically interacts with the erythropoietin receptor and enhances Jak2-mediated signaling
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Calmodulin physically interacts with the erythropoietin receptor and enhances Jak2-mediated signaling
چکیده انگلیسی
Stimulation of the erythropoietin receptor (EpoR) induces a transient increase in intracellular Ca2+ level as well as activation of the Jak2 tyrosine kinase to stimulate various downstream signaling pathways. Here, we demonstrate that the universal Ca2+ receptor calmodulin (CaM) binds EpoR in a Ca2+-dependent manner in vitro. Binding studies using various EpoR mutants in hematopoietic cells showed that CaM binds the membrane-proximal 65-amino-acid cytoplasmic region (amino acids 258-312) of EpoR that is critical for activation of Jak2-mediated EpoR signaling. Structurally unrelated CaM antagonists, W-13 and CMZ, inhibited activation of Jak2-mediated EpoR signaling pathways, whereas W-12, a W-13 analog, did not show any significant inhibitory effect. Moreover, overexpression of CaM augmented Epo-induced tyrosine phosphorylation of the EpoR. W-13, but not W-12, also inhibited Epo-induced proliferation and survival. Together, these results indicate that CaM binds to the membrane-proximal EpoR cytoplasmic region and plays an essential role in activation of Jak2-mediated EpoR signaling.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 335, Issue 2, 23 September 2005, Pages 424-431
نویسندگان
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