Regulation of collagen fibrillogenesis by cell-surface expression of kinase dead DDR2.
Regulation of collagen fibrillogenesis by cell-surface expression of kinase dead DDR2.
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DOI：
10.1016/j.jmb.2008.10.060
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发表时间：
2009-01-23
影响因子：
5.6
通讯作者：
Agarwal, Gunjan
中科院分区：
文献类型：
--
作者：
Blissett, Angela R.;Garbellini, Derek;Calomeni, Edward P.;Mihai, Cosmin;Elton, Terry S.;Agarwal, Gunjan
The assembly of collagen fibers, the major component of the extracellular matrix (ECM), governs a variety of physiological processes. Collagen fibrillogenesis is a tightly controlled process in which several factors including collagen binding proteins play a crucial role. Discoidin domain receptors (DDR1 and DDR2) are receptor tyrosine kinases that bind to and get phosphorylated upon collagen binding. The phosphorylation of DDRs is known to activate matrix metalloproteases, which in turn cleave the ECM. In our earlier studies, we established a novel mechanism of collagen regulation by DDRs, that is, the extracellular domain (ECD) of DDR2, when used as a purified, soluble protein, inhibits collagen fibrillogenesis in-vitro. To extend this novel observation, the current study investigates how the DDR2-ECD, when expressed as a membrane anchored, cell-surface protein, affects collagen fibrillogenesis by cells. We generated a mouse osteoblast cell line which stably expresses a kinase deficient form of DDR2, termed DDR2/-KD, on its cell surface. Transmission electron microscopy, fluorescence microscopy and hydroxyproline assays demonstrated that the expression of DDR2/-KD not only reduced the rate and abundance of collagen deposition but also induced significant morphological changes in the resulting fibers. Taken together, our observations extend the functional roles that DDR2 and possibly other membrane anchored collagen binding proteins can play in the regulation of cell adhesion, migration, proliferation and in the remodeling of the extracellular matrix.
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影响因子：
8.8
作者：
通讯作者：
--
影响因子：
5.6
作者：
Agarwal, Gunjan;Mihai, Cosmin;Iscru, Daniel F.
通讯作者：
Iscru, Daniel F.
影响因子：
4.8
作者：
Notbohm, H;Nokelainen, M;Kivirikko, KI
通讯作者：
Kivirikko, KI
影响因子：
6.2
作者：
Pornprasertsuk, S;Duarte, WR;Yamauchi, M
通讯作者：
Yamauchi, M
影响因子：
3.6
作者：
CONTARD, P;JACOBS, L;FLEISCHMAJER, R
通讯作者：
FLEISCHMAJER, R