کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1964905 1058632 2007 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
MEK1 activation by PAK: A novel mechanism
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
MEK1 activation by PAK: A novel mechanism
چکیده انگلیسی

Extracellular signal-Regulated Kinase (ERK) controls a variety of cellular processes, including cell proliferation and cell motility. While oncogenic mutations in Ras and B-Raf result in deregulated ERK activity and proliferation and migration in some tumor cells, other tumors exhibit elevated ERK signaling in the absence of these mutations. Here we provide evidence that PAK can directly activate MEK1 by a mechanism distinct from conventional Ras/Raf mediated activation. We find that PAK phosphorylation of MEK1 serine 298 stimulates MEK1 autophosphorylation on the activation loop, and activation of MEK1 activity towards ERK in in vitro reconstitution experiments. Serines 218 and/or 222 in the MEK1 activation loop are required for PAK-stimulated MEK1 activity towards ERK. MEK2, which is a poor target for PAK phosphorylation in cells, is not activated in this manner. Tissue culture experiments verify that this mechanism is used in suspended fibroblasts expressing mutationally activated PAK1. We speculate that aberrant signaling through PAK may directly induce anchorage-independent MEK1 activation in tumor cells lacking oncogenic Ras or Raf mutations, and that this mechanism may contribute to localized MEK signaling in focal contacts and adhesions during cell adhesion or migration.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 19, Issue 7, July 2007, Pages 1488–1496
نویسندگان
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