Receptor tyrosine kinases (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. The protein encoded by this gene is a RTK that is widely expressed in normal and transformed epithelial cells and is activated by various types of collagen. This protein belongs to a subfamily of tyrosine kinase receptors with a homology region to the Dictyostelium discoideum protein discoidin I in their extracellular domain. Its autophosphorylation is achieved by all collagens so far tested (type I to type VI). A closely related family member is the DDR2 protein. In situ studies and Northern-blot analysis showed that expression of this encoded protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, this protein is significantly over-expressed in several human tumors from breast, ovarian, esophageal, and pediatric brain. This gene is located on chromosome 6p21.3 in proximity to several HLA class I genes. Alternative splicing of this gene results in multiple transcript variants.
Edelhoff S, Sweetser DA, Disteche CM (Jan 1995). "Mapping of the NEP receptor tyrosine kinase gene to human chromosome 6p21.3 and mouse chromosome 17C". Genomics. 25 (1): 309–11. doi:10.1016/0888-7543(95)80144-B. PMID7774938.
Shelling AN, Butler R, Jones T, Laval S, Boyle JM, Ganesan TS (Jan 1995). "Localization of an epithelial-specific receptor kinase (EDDR1) to chromosome 6q16". Genomics. 25 (2): 584–7. doi:10.1016/0888-7543(95)80065-T. PMID7789998.
Weiner TM, Liu ET, Craven RJ, Cance WG (Jan 1994). "Expression of growth factor receptors, the focal adhesion kinase, and other tyrosine kinases in human soft tissue tumors". Annals of Surgical Oncology. 1 (1): 18–27. doi:10.1007/BF02303537. PMID7834423.
Laval S, Butler R, Shelling AN, Hanby AM, Poulsom R, Ganesan TS (Nov 1994). "Isolation and characterization of an epithelial-specific receptor tyrosine kinase from an ovarian cancer cell line". Cell Growth & Differentiation. 5 (11): 1173–83. PMID7848919.
Di Marco E, Cutuli N, Guerra L, Cancedda R, De Luca M (Nov 1993). "Molecular cloning of trkE, a novel trk-related putative tyrosine kinase receptor isolated from normal human keratinocytes and widely expressed by normal human tissues". The Journal of Biological Chemistry. 268 (32): 24290–5. PMID8226977.
Perez JL, Shen X, Finkernagel S, Sciorra L, Jenkins NA, Gilbert DJ, Copeland NG, Wong TW (Jan 1994). "Identification and chromosomal mapping of a receptor tyrosine kinase with a putative phospholipid binding sequence in its ectodomain". Oncogene. 9 (1): 211–9. PMID8302582.
Perez JL, Jing SQ, Wong TW (Apr 1996). "Identification of two isoforms of the Cak receptor kinase that are coexpressed in breast tumor cell lines". Oncogene. 12 (7): 1469–77. PMID8622863.
Valent A, Meddeb M, Danglot G, Duverger A, Nguyen VC, Bernheim A (Jul 1996). "Assignment of the NTRK4 (trkE) gene to chromosome 6p21". Human Genetics. 98 (1): 12–5. doi:10.1007/s004390050152. PMID8682498.
Playford MP, Butler RJ, Wang XC, Katso RM, Cooke IE, Ganesan TS (Jul 1996). "The genomic structure of discoidin receptor tyrosine kinase". Genome Research. 6 (7): 620–7. doi:10.1101/gr.6.7.620. PMID8796349.
Sakuma S, Saya H, Tada M, Nakao M, Fujiwara T, Roth JA, Sawamura Y, Shinohe Y, Abe H (Dec 1996). "Receptor protein tyrosine kinase DDR is up-regulated by p53 protein". FEBS Letters. 398 (2-3): 165–9. doi:10.1016/S0014-5793(96)01234-3. PMID8977099.
Nemoto T, Ohashi K, Akashi T, Johnson JD, Hirokawa K (1998). "Overexpression of protein tyrosine kinases in human esophageal cancer". Pathobiology. 65 (4): 195–203. doi:10.1159/000164123. PMID9396043.
Tanaka K, Nagayama Y, Nakano T, Takamura N, Namba H, Fukada S, Kuma K, Yamashita S, Niwa M (Mar 1998). "Expression profile of receptor-type protein tyrosine kinase genes in the human thyroid". Endocrinology. 139 (3): 852–8. doi:10.1210/en.139.3.852. PMID9492013.
Shrivastava A, Radziejewski C, Campbell E, Kovac L, McGlynn M, Ryan TE, Davis S, Goldfarb MP, Glass DJ, Lemke G, Yancopoulos GD (Dec 1997). "An orphan receptor tyrosine kinase family whose members serve as nonintegrin collagen receptors". Molecular Cell. 1 (1): 25–34. doi:10.1016/S1097-2765(00)80004-0. PMID9659900.
Vogel W, Brakebusch C, Fässler R, Alves F, Ruggiero F, Pawson T (Feb 2000). "Discoidin domain receptor 1 is activated independently of beta(1) integrin". The Journal of Biological Chemistry. 275 (8): 5779–84. doi:10.1074/jbc.275.8.5779. PMID10681566.
Foehr ED, Tatavos A, Tanabe E, Raffioni S, Goetz S, Dimarco E, De Luca M, Bradshaw RA (May 2000). "Discoidin domain receptor 1 (DDR1) signaling in PC12 cells: activation of juxtamembrane domains in PDGFR/DDR/TrkA chimeric receptors". FASEB Journal. 14 (7): 973–81. PMID10783152.
Weiner HL, Huang H, Zagzag D, Boyce H, Lichtenbaum R, Ziff EB (Dec 2000). "Consistent and selective expression of the discoidin domain receptor-1 tyrosine kinase in human brain tumors". Neurosurgery. 47 (6): 1400–9. doi:10.1097/00006123-200012000-00028. PMID11126911.
Mohan RR, Mohan RR, Wilson SE (Jan 2001). "Discoidin domain receptor (DDR) 1 and 2: collagen-activated tyrosine kinase receptors in the cornea". Experimental Eye Research. 72 (1): 87–92. doi:10.1006/exer.2000.0932. PMID11133186.