Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10770844 | Biochemical and Biophysical Research Communications | 2005 | 8 Pages |
Abstract
Mechanical forces can induce differentiation of fibroblasts into myofibroblasts, a process which requires activation of the MAP kinase p38. Currently, the identification of other phospho-kinases involved in myofibroblast differentiation has not been explored. We applied static tensile forces to rat cardiac fibroblasts via collagen-coated magnetite beads and examined activation of protein phospho-kinases by the Kinexus phospho-antibody screening system. Of 75 candidate protein kinases screened, 39 were detected and, of these, 31 phospho-kinases were analyzed. Following force application, 12 out of 31 phospho-kinases exhibited increases of phosphorylation including PKR (>4-fold), MKK3 (3-fold), MKK6 (â¼2-fold), and p38 (â¼2-fold). In several types of mechanically sensitive, contractile fibroblasts including rat cardiac, human gingival, and Rat-2 fibroblasts, tensile forces increased eIF-2α phosphorylation, a downstream effector of PKR. We conclude that phospho-antibody screening is an efficient method for discovery of novel mechanical force-induced phospho-kinases and force can activate eIF-2α phospho-kinases in fibroblasts.
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Authors
J. Wang, Carol Laschinger, Xiao Han Zhao, Baldwin Mak, A. Seth, C.A. McCulloch,