کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5918080 | 1163825 | 2008 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
SKAP55 modulates T cell antigen receptor-induced activation of the Ras-Erk-AP1 pathway by binding RasGRP1
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی مولکولی
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چکیده انگلیسی
Src kinase-associated phosphoprotein of 55 kDa (SKAP55) is an adapter protein with an N-terminal region, a pleckstrin homology domain, a linker with tyrosine phosphorylation sites, and a C-terminal Src homology 3 domain. We report that overexpression of SKAP55 disrupts signaling from the TCR to the Ras-Erk-AP-1 pathway and transcription of the IL-2 gene in primary human T cells and in Jurkat T leukemia cells. In contrast, moderate overexpression of SKAP55 increased TCR-dependent AP-1 transcriptional activity, suggesting that high-level SKAP55 overexpression interfered with the assembly of functional signaling complexes required for TCR coupling to the Ras pathway. In support of this view, knock-down of SKAP55 by RNA interference resulted in decreased reporter gene activation and decreased ERK phosphorylation. In contrast, TCR-induced NF-κB activation was not affected. Since constitutively active forms of Ras or Raf-1 overcame the inhibitory effects of SKAP55 overexpression, we searched for a mechanism upstream of Ras and found that SKAP55 co-immunoprecipitated with the Ras activator RasGRP1. The binding of RasGRP1 to SKAP55 required the C-terminus of SKAP55 and was enhanced by tyrosine phosphorylation of SKAP55. These results suggest that SKAP55 modulates signal transduction from the TCR to Ras by binding to RasGRP1.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 45, Issue 2, January 2008, Pages 510-522
Journal: Molecular Immunology - Volume 45, Issue 2, January 2008, Pages 510-522
نویسندگان
Karena A. Kosco, Fabio Cerignoli, Scott Williams, Robert T. Abraham, Tomas Mustelin,