Biology:Discoidin domain-containing receptor 2

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Discoidin domain-containing receptor 2, also known as CD167b (cluster of differentiation 167b), is a protein that in humans is encoded by the DDR2 gene. Discoidin domain-containing receptor 2 is a receptor tyrosine kinase (RTK).

Function

RTKs play a key role in the communication of cells with their microenvironment. These molecules are involved in the regulation of cell growth, differentiation, and metabolism. In several cases the biochemical mechanism by which RTKs transduce signals across the membrane has been shown to be ligand induced receptor oligomerization and subsequent intracellular phosphorylation. In the case of DDR2, the ligand is collagen which binds to its extracellular discoidin domain. This autophosphorylation leads to phosphorylation of cytosolic targets as well as association with other molecules, which are involved in pleiotropic effects of signal transduction. DDR2 has been associated with a number of diseases including fibrosis and cancer.

Structure

RTKs have a tripartite structure with extracellular, transmembrane, and cytoplasmic regions. This gene encodes a member of a novel subclass of RTKs and contains a distinct extracellular region encompassing a factor VIII-like domain.

Gene

Alternative splicing in the 5' UTR of the DDR2 gene results in multiple transcript variants encoding the same protein.

Interactions

DDR2 (gene) has been shown to interact with SHC1 and phosphorylate Shp2. DDR2 also interacts with Integrin α₁β₁ and α₂β₁ by promoting their adhesion to collagen.

Further reading

• "Chromosomal location of the human transketolase gene". Cytogenet. Cell Genet. 61 (4): 274–5. 1992. doi:10.1159/000133421. PMID 1486804. 
• "Nucleotide and predicted amino acid sequence of a cDNA clone encoding part of human transketolase". Biochem. Biophys. Res. Commun. 183 (3): 1159–66. 1992. doi:10.1016/S0006-291X(05)80312-2. PMID 1567394. 
• "Mapping of the NEP receptor tyrosine kinase gene to human chromosome 6p21.3 and mouse chromosome 17C". Genomics 25 (1): 309–11. 1995. doi:10.1016/0888-7543(95)80144-B. PMID 7774938. 
• "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• "Structure, expression and chromosomal mapping of TKT from man and mouse: a new subclass of receptor tyrosine kinases with a factor VIII-like domain". Oncogene 8 (12): 3433–40. 1993. PMID 8247548. 
• "Generation and analysis of 280,000 human expressed sequence tags". Genome Res. 6 (9): 807–28. 1996. doi:10.1101/gr.6.9.807. PMID 8889549. 
• "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• "The discoidin domain receptor tyrosine kinases are activated by collagen". Mol. Cell 1 (1): 13–23. 1997. doi:10.1016/S1097-2765(00)80003-9. PMID 9659899. 
• "Discoidin domain receptor (DDR) 1 and 2: collagen-activated tyrosine kinase receptors in the cornea". Exp. Eye Res. 72 (1): 87–92. 2001. doi:10.1006/exer.2000.0932. PMID 11133186. 
• "Discoidin domain receptor 2 interacts with Src and Shc following its activation by type I collagen". J. Biol. Chem. 277 (21): 19206–12. 2002. doi:10.1074/jbc.M201078200. PMID 11884411. 
• "An extracellular matrix-specific microarray allowed the identification of target genes downstream of discoidin domain receptors". Matrix Biol. 22 (4): 373–81. 2003. doi:10.1016/S0945-053X(03)00053-2. PMID 12935821. 
• "Role of discoidin domain receptors 1 and 2 in human smooth muscle cell-mediated collagen remodeling: potential implications in atherosclerosis and lymphangioleiomyomatosis". Am. J. Pathol. 164 (5): 1575–85. 2004. doi:10.1016/S0002-9440(10)63716-9. PMID 15111304. 
• "The D2 period of collagen II contains a specific binding site for the human discoidin domain receptor, DDR2". J. Mol. Biol. 344 (4): 993–1003. 2004. doi:10.1016/j.jmb.2004.09.089. PMID 15544808. 
• "Discoidin domain receptor 2 mediates tumor cell cycle arrest induced by fibrillar collagen". J. Biol. Chem. 280 (48): 40187–94. 2005. doi:10.1074/jbc.M508226200. PMID 16186104. 
• "Tyrosine 740 phosphorylation of discoidin domain receptor 2 by Src stimulates intramolecular autophosphorylation and Shc signaling complex formation". J. Biol. Chem. 280 (47): 39058–66. 2005. doi:10.1074/jbc.M506921200. PMID 16186108. 
• "The discoidin domain receptor DDR2 is a receptor for type X collagen". Matrix Biol. 25 (6): 355–64. 2006. doi:10.1016/j.matbio.2006.05.006. PMID 16806867. 
• "Expression of discoidin domain receptor 2 (DDR2) extracellular domain in pichia pastoris and functional analysis in synovial fibroblasts and NIT3T3 cells". Mol. Cell. Biochem. 290 (1–2): 43–53. 2006. doi:10.1007/s11010-006-9136-4. PMID 16967187. 
• "Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma". Br. J. Cancer 96 (5): 808–14. 2007. doi:10.1038/sj.bjc.6603614. PMID 17299390. 
• "Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice". Arthritis Rheum. 62 (9): 2736–44. 2010. doi:10.1002/art.27582. PMID 20518074. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.