Discoidin domain-containing receptor 2

Definition:

Tyrosine kinase involved in the regulation of tissues remodeling. It functions as cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing.

References:

[1]. W Vogel, et al. The discoidin domain receptor tyrosine kinases are activated by collagen. Mol Cell. 1997 Dec;1(1):13-23. [Content Brief]

[2]. Federico Carafoli, et al. Crystallographic insight into collagen recognition by discoidin domain receptor 2. Structure. 2009 Dec 9;17(12):1573-1581. [Content Brief]

[3]. Steven J Wall, et al. Discoidin domain receptor 2 mediates tumor cell cycle arrest induced by fibrillar collagen. J Biol Chem. 2005 Dec 2;280(48):40187-94. [Content Brief]

[4]. Linda Xu, et al. Recurrent, Activating Variants in the Receptor Tyrosine Kinase DDR2 Cause Warburg-Cinotti Syndrome. Am J Hum Genet. 2018 Dec 6;103(6):976-983. [Content Brief]

[5]. Antonios D Konitsiotis, et al. Characterization of high affinity binding motifs for the discoidin domain receptor DDR2 in collagen. J Biol Chem. 2008 Mar 14;283(11):6861-8. [Content Brief]

[6]. Kuan-Liang Lin, et al. Transcriptional upregulation of DDR2 by ATF4 facilitates osteoblastic differentiation through p38 MAPK-mediated Runx2 activation. J Bone Miner Res. 2010 Nov;25(11):2489-503. [Content Brief]

[7]. Lin Xu, et al. Increased expression of the collagen receptor discoidin domain receptor 2 in articular cartilage as a key event in the pathogenesis of osteoarthritis. Arthritis Rheum. 2007 Aug;56(8):2663-73. [Content Brief]

[8]. Yan Zhang, et al. An essential role of discoidin domain receptor 2 (DDR2) in osteoblast differentiation and chondrocyte maturation via modulation of Runx2 activation. J Bone Miner Res. 2011 Mar;26(3):604-17. [Content Brief]

[9]. Kyungmi Yang, et al. Tyrosine 740 phosphorylation of discoidin domain receptor 2 by Src stimulates intramolecular autophosphorylation and Shc signaling complex formation. J Biol Chem. 2005 Nov 25;280(47):39058-66. [Content Brief]

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