Epithelial discoidin domain-containing receptor
FunctionEpithelial discoidin domain-containing receptor (DDR1 and DDR2) are extracellular matrix-sensing Receptor tyrosine kinases which are activated by collagen and are expressed in bronchial epithelium. They are responsible for maintaining the normal structure of skin and kidney epithelia[1]. DDR1 and DDR2 function as sensors for extracellular matrix and to regulate a wide range of cell functions from migration and proliferation to cytokine secretion and extracellular matrix homeostasis/remodeling[2]. See also Kinase-linked, enzyme-linked and related receptors. DiseaseDDR1 promotes inflammation in atherosclerosis, lung fibrosis and kidney injury[2] RelevanceDDR1 plays a consequential role in a variety of cancers[3]. A low DDR1/high DDR2 profile is associated with high tumor grade and may identify invasive carcinomas with worse prognosis[4]. Structural highlightsDDR1 contains a discoidin domain. This domain is about 150 amino acid long and is found in many blood coagulation factors. The structure of the shows hydrogen bonds interactions between the anti-cancer drug and the kinase domain including bonds with the [5]. Water molecules are shown as red spheres.
|
| ||||||||||
3D structures of epithelial discoidin domain-containing receptor3D structures of epithelial discoidin domain-containing receptor
Updated on 19-January-2022
ReferencesReferences
- ↑ Roberts ME, Magowan L, Hall IP, Johnson SR. Discoidin domain receptor 1 regulates bronchial epithelial repair and matrix metalloproteinase production. Eur Respir J. 2011 Jun;37(6):1482-93. doi: 10.1183/09031936.00039710. Epub 2010, Sep 30. PMID:20884741 doi:http://dx.doi.org/10.1183/09031936.00039710
- ↑ 2.0 2.1 Borza CM, Pozzi A. Discoidin domain receptors in disease. Matrix Biol. 2014 Feb;34:185-92. doi: 10.1016/j.matbio.2013.12.002. Epub 2013 Dec, 19. PMID:24361528 doi:http://dx.doi.org/10.1016/j.matbio.2013.12.002
- ↑ Song J, Chen X, Bai J, Liu Q, Li H, Xie J, Jing H, Zheng J. Discoidin domain receptor 1 (DDR1), a promising biomarker, induces epithelial to mesenchymal transition in renal cancer cells. Tumour Biol. 2016 Aug;37(8):11509-21. doi: 10.1007/s13277-016-5021-2. Epub 2016, Mar 28. PMID:27020590 doi:http://dx.doi.org/10.1007/s13277-016-5021-2
- ↑ Toy KA, Valiathan RR, Nunez F, Kidwell KM, Gonzalez ME, Fridman R, Kleer CG. Tyrosine kinase discoidin domain receptors DDR1 and DDR2 are coordinately deregulated in triple-negative breast cancer. Breast Cancer Res Treat. 2015 Feb;150(1):9-18. doi: 10.1007/s10549-015-3285-7., Epub 2015 Feb 10. PMID:25667101 doi:http://dx.doi.org/10.1007/s10549-015-3285-7
- ↑ Canning P, Tan L, Chu K, Lee SW, Gray NS, Bullock AN. Structural mechanisms determining inhibition of the collagen receptor DDR1 by selective and multi-targeted type II kinase inhibitors. J Mol Biol. 2014 Apr 22. pii: S0022-2836(14)00198-3. doi:, 10.1016/j.jmb.2014.04.014. PMID:24768818 doi:http://dx.doi.org/10.1016/j.jmb.2014.04.014