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KMID : 1161520140180060372
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Animal Cells and Systems
2014 Volume.18 No. 6 p.372 ~ p.379
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Role of the intracellular juxtamembrane domain of discoidin domain receptor 2 in focal adhesion formation
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You Eun-Ae
Park So-Yeon
Kim Dae-Hwan
Jung Jang-Ho
Ko Pan-Seon
Park Chan-Mi
Rhee Sang-Myung
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Abstract
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Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase that is activated by collagen instead of soluble growth factors. Activated DDR2 is associated with cell adhesion and migration. However, the detailed molecular mechanism by which DDR2-mediated cell-matrix interactions occur is yet to be fully elucidated. In this study, we demonstrate that the assembly of focal adhesions is enhanced by ectopic expression of DDR2, following collagen stimulation, while the expression of a catalytic activity defect mutant impaired DDR2-mediated focal adhesion formation. Additionally, overexpression of various truncated mutants showed that the juxtamembrane 2 (JM2) domain of DDR2 is essential for increased formation of focal adhesions. Overexpression of the isolated JM2 domain in mouse embryonic fibroblasts (MEFs), which abundantly express endogenous DDR2, inhibited formation of focal adhesions in response to collagen stimulation. Furthermore, an overexpression of JM2 domain decreased collagen-induced phosphorylation of myosin light chain (MLC), suggesting that JM2-mediated signaling is likely to be important for focal adhesion formation. Using affinity chromatography analysis and a pull-down assay, we found that an interaction between JM2 and nonmuscle myosin IIA enables phosphorylation of MLC by DDR2. Thus, our results suggest that this interaction may provide a mechanism for DDR2-mediated focal adhesion formation in response to collagen stimulation.
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KEYWORD
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discoidin domain receptor 2, focal adhesion, myosin II, intracellular juxamembrane domain, collagen
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