Poster abstracts

Poster number 12 submitted by Angela Blissett

Regulation of Collagen Fibrillogenesis by Kinase-Dead DDR2

Angela Blissett (OSU Biophsyics Program), Derek Garbellini (Davis Heart and Lung Institute, OSU), Edward Calomeni (Department of Pathology, OSU), Cosmin Mihai (OSU Biophysics Program), Terry S. Elton (Davis Heart and Lung Institute and College of Pharmacy, OSU), Gunjan Agarwal (DHLRI, OSU Biophysics Program and Department of Biomedical Engineering)

Abstract:
The assembly and degradation of collagen fibers is a complex process regulated by several factors including collagen binding proteins (CBPs). Little is understood about how cell-membrane anchored CBPs affect the assembly of collagen fibrils (fibrillogenesis). In our earlier work we demonstrated that the CBPs, Discoidin Domain Receptors (DDR1 and DDR2) affect the kinetics and morphology of collagen fibrils (1,2) in vitro. In this work we elucidate how membrane anchored DDR2 regulates collagen fibrillogenesis for endogenously secreted collagen in mammalian cells. Our work employs a kinase-dead variant of DDR2, thus signifying a functional role of even kinase-dead isoforms of DDR receptor tyrosine kinases. Although several naturally occurring splice variants for DDR1 have been identified (3), kinase dead isoforms of DDR2 are thus far uncharacterized. Our studies reveal the importance of characterizing the multiple mRNA species for DDR2 reported in several mammalian tissues (4,5).

References:
(1) Mihai, C., Iscru, D.F., Druhan, L.J., Elton, T.S., Agarwal, G., (2006) JMB, 361, 864-876
(2) Agarwal, G., Mihai, C., Iscru, D.F., (2007) JMB, 367, 443-455
(3) Alves, F., Saupe, S., Ledwon, M., Schaub, F., Hiddemann, W. and Vogel, W. F. (2001) FASEB J. 15(7), 1321-3
(4) Alves, F., Vogel, W., Mossie, K., Millauer, B., Hofler, H., Ullrich, A., (1995) Oncogene, 10(3), 609-18
(5) Ferri, N., Carragher. N.O., Raines, E.W., (2004) J. Pathol., 164(5), 1575-85

Keywords: DDR2, collagen fibrillogenesis, TEM