New behavior study findings have been published by E.J. Joslin and colleagues
2008 JAN 14 -- According to a study from the United States, "EGF family ligands are synthesized as membrane-anchored precursors whose proteolytic release yields mature diffusible factors that can activate cell surface receptors in autocrine or paracrine mode. Expression of these ligands is altered in pathological states and in physiological processes, such as development and tissue regeneration." "Despite the widely documented biological importance of autocrine EGF signaling, quantitative relationships between protease- mediated ligand release and consequent cell behavior have not been rigorously investigated. We thus explored the relationship between autocrine EGF release rates and cell behavioral responses along with activation of ERK, a key downstream signal, by expressing chimeric ligand precursors and modulating their proteolytic shedding using a metalloprotease inhibitor in human mammary epithelial cells. We found that ERK activation increased monotonically with increasing ligand release rate despite concomitant downregulation of EGF receptor levels. Cell migration speed was directly related to ligand release rate and proportional to steady- state phospho- ERK levels. Moreover, migration speed was significantly greater for autocrine stimulation compared with exogenous stimulation, even at comparable phospho-ERK levels. By contrast, cell proliferation rates were approximately equivalent at all ligand release rates and were similar regardless of whether the ligand was presented endogenously or exogenously," wrote E.J. Joslin and colleagues. The researchers concluded: "Thus, in our mammary epithelial cell system, migration and proliferation are differentially sensitive to the mode of EGF ligand presentation." Joslin and colleagues published their study in the Journal of Cell Science (EGF-receptor-mediated mammary epithelial cell migration is driven by sustained ERK signaling from autocrine stimulation. Journal of Cell Science, 2007;120(20):3688-3699). For more information, contact D.A. Lauffenburger, MIT, Dept. of Biology Engineering, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Publisher contact information for the Journal of Cell Science is: Company of Biologists Ltd., Bidder Building Cambridge Commercial Park Cowley Rd., Cambridge CB4 4DL, Cambs, England. Keywords: United States, Cambridge, Behavior, Cell Motility, Cell Proliferation, Cell Science, Enzymology, Physiology, Protease, Tissue Regeneration. This article was prepared by Proteomics Weekly editors from staff and other reports. Copyright 2008, Proteomics Weekly via NewsRx.com.
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