کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1938261 1050736 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Sequential processing of the transmembrane chemokines CX3CL1 and CXCL16 by α- and γ-secretases
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Sequential processing of the transmembrane chemokines CX3CL1 and CXCL16 by α- and γ-secretases
چکیده انگلیسی

The chemokines CX3CL1/Fractalkine and CXCL16 are expressed as transmembrane molecules and can mediate cell–cell-adhesion. By proteolytic processing, CX3CL1 and CXCL16 are released from the cell surface by proteolytic shedding resulting in the generation of soluble chemoattractants. This ectodomain release is mediated by the α-secretase-like activity of the two disintegrins and metalloproteinases ADAM10 and ADAM17. Using CX3CL1 and CXCL16 constructs C-terminally fused to two Z-domains of Protein A (2Z-tag) we detect C-terminal fragments (CTFs) of both chemokines resulting from ADAM10-mediated cleavages at multiple sites as examined by inhibitor studies. Furthermore, inhibitor studies as well as genetic studies using presenilin 1/2-deficient cell lines suggest the involvement of γ-secretase-but not β-secretase-like activity in the processing of transmembrane chemokines. The combination of α- and γ-secretase and proteasomal inhibitors points towards a sequential processing of transmembrane chemokines by first ADAM10 and then γ-secretases and possible further degradation. This proteolytic processing cascade of transmembrane chemokines is similar to that described for Notch and E-cadherin where CTFs generated by γ-secretase serve as intracellular signal transmitters.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 358, Issue 1, 22 June 2007, Pages 233–240
نویسندگان
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