کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1964153 1058529 2007 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
PI3Kγ is the dominant isoform involved in migratory responses of human T lymphocytes: Effects of ex vivo maintenance and limitations of non-viral delivery of siRNA
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
PI3Kγ is the dominant isoform involved in migratory responses of human T lymphocytes: Effects of ex vivo maintenance and limitations of non-viral delivery of siRNA
چکیده انگلیسی

Use of mice in which individual PI3K isoforms have been deleted or mutated by gene targeting, has determined that PI3Kγ provides a key migratory signal for T lymphocyte migration. Since PI3Kγ can be a dispensable signal for directional migration of human T cells, we have adopted a pharmacological and siRNA strategy to assess the contribution of individual PI3K isoforms to chemokine-stimulated migration of human T cells. The broad spectrum PI3K isoform inhibitor Ly294002 inhibits CXCL12-stimulated migration of freshly isolated T lymphocytes. Use of second generation inhibitors that can discriminate between individual PI3K isoforms, revealed that PI3Kγ was the major contributor to CXCL12-induced migration and PI3K/Akt signaling (as assessed by S6 phosphorylation). Non-viral delivery of siRNA targeting class I (PI3Kγ), class II (PI3KC2α and PI3KC2β) and class III PI3Ks, followed by 3 days ex vivo culture, reduces the levels of isoform mRNA, but is insufficient to impact on cell migration responses. However, ex vivo maintenance of T cells alone, independently of siRNA treatment, resulted in the migratory response of T cells toward CXCL12 becoming insensitive to Ly294002. Remarkably, random migration remains sensitive to Ly294002. This study therefore, highlights that the migratory response of freshly isolated human T cells is dependent on PI3K signals that are provided predominantly by PI3Kγ. However, the role of PI3K in cell migration is context-dependent and diminishes during ex vivo maintenance.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 19, Issue 12, December 2007, Pages 2528–2539
نویسندگان
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