Journal
EXPERIMENTAL CELL RESEARCH
Volume 300, Issue 2, Pages 259-271Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2004.06.033
Keywords
extracellular matrix; spreading; hepatocyte; myosin; ATPase; tension; cyclin D1; ERK; cell cycle
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Cell spreading and proliferation are tightly Coupled in anchorage-dependent cells. While adhesion-dependent proliferation signals require ail intact actin cytoskeleton, and some of these signals such as ERK activation have been characterized, the role of myosin in spreading and cell cycle progression under different extracellular matrix (ECM) conditions is not known. Studies presented here examine changes in myosin activity in freshly isolated hepatocytes under ECM conditions that promote either proliferation (high fibronectin density) or growth arrest (low fibronectin density). Three different measures were obtained and related to both spreading and cell cycle progression: myosin protein levels and association with cytoskeleton, myosin light chain phosphorylation, and its ATPase activity. During the first 48 h in culture, corresponding with transit through G1 phase, there was a six-fold increase in both myosin protein levels and myosin association with actin cytoskeleton. There was also a steady increase in myosin light chain phosphorylation and ATPase activity with spreading, which did not occur in non-spread, growth-arrested cells oil low density of fibronectin. Myosin-inhibiting drugs blocked ERK activation, cyclin D1 expression, and S phase entry. Overexpression of the cell cycle protein cyclin D1 overcame both ECM-dependent and actomyosin-dependent inhibition of DNA synthesis, Suggesting that cyclin D1 is a key event downstream of myosin-dependent cell cycle regulation. (C) 2004 Elsevier Inc. All rights reserved.
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