کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1964614 1058562 2006 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Fyn kinase acts upstream of Shp2 and p38 mitogen-activated protein kinase to promote chemotaxis of mast cells towards stem cell factor
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Fyn kinase acts upstream of Shp2 and p38 mitogen-activated protein kinase to promote chemotaxis of mast cells towards stem cell factor
چکیده انگلیسی

The c-Kit receptor protein–tyrosine kinase plays a critical role in the differentiation, growth and survival of mast cells. Binding of its ligand stem cell factor (SCF), induces c-Kit dimerization, autophosphorylation, and recruitment of signaling proteins. The juxtamembrane sequence of c-Kit contains recruitment sites for the Src family kinases Fyn and Lyn, as well as Shp1 and Shp2 protein–tyrosine phosphatases. To characterize the role of Fyn in c-Kit signaling, we generated bone marrow-derived mast cells (BMMCs) from wild-type and Fyn knock-out mice. In contrast with previous studies of Lyn-deficient BMMCs, SCF treatment of Fyn-deficient BMMCs revealed no overt defects in the overall pattern of tyrosine phosphorylation, phosphatidylinositol 3′ kinase recruitment to c-Kit, or phosphorylation of Stat3 transcription factor. However, Fyn-deficient mast cells showed a significant reduction in phosphorylation of Shp2 phosphatase and p38 mitogen-activated protein kinase. Defects in Shp2 and p38 phosphorylation were restored in Fyn-deficient mast cells transduced with a Fyn-expressing retrovirus (Fyn-rescue). Fyn-deficient BMMCs displayed reduced chemotaxis towards SCF, and this defect was corrected in Fyn-rescue cells. This study provides evidence that recruitment of both Shp2 and Fyn to juxtamembrane sites in c-Kit results in Shp2 phosphorylation, downstream signaling to p38 mitogen-activated protein kinase, and enhanced chemotaxis of mast cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 18, Issue 9, September 2006, Pages 1447–1454
نویسندگان
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