Recombinant Human DDR1 Fc Chimera Protein, CF 50 UG

• Purity

  >85%, by SDS-PAGE under reducing conditions and visualized by silver stain

• Endotoxin Level

  <0.01 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by its ability to bind Collagen I in a functional ELISA. Leitinger, B. (2003) J. Biol. Chem.     278:16761. Immobilized Collagen I at 10 µg/mL (100 µL/well) can bind rhDDR1 with an apparent K    _D <10 nM.    
  Optimal dilutions should be determined by each laboratory for each application.  

• Source

  Mouse myeloma cell line, NS0-derived

  Human DDR1 (Asp21 - Thr416) Accession # Q5ST11	IEGRMD	Human IgG1 (Pro100 - Lys330)
  N-terminus		C-terminus

• Accession #

• N-terminal Sequence    
  Analysis

  Asp21

• Structure / Form

  Disulfide-linked homodimer

• Predicted Molecular Mass

  70.5 kDa (monomer)

• SDS-PAGE

  90-95 kDa, reducing conditions

Background: DDR1

DDR1, also known as CAK, CD167a, RTK6, and TrkE, is a 120 - 140 kDa type I transmembrane glycoprotein that belongs to the discoidin-like domain containing subfamily of receptor tyrosine kinases (1, 2). Mature human DDR2 consists of a 398 amino acid (aa) extracellular domain (ECD) that includes the discoidin-like domain, a 27 aa transmembrane segment, and a 470 aa cytoplasmic region with a tyrosine kinase domain (3). Within the ECD, human DDR1 shares 53% aa sequence identity with human DDR2 and 93% with mouse and rat DDR1. DDR1 is expressed on epithelial tissues, activated monocytes and neutrophils, and in several cancers (2, 4). Compared to isoform DDR1b, DDR1a lacks 37 aa’s that include a Shc-interacting NPxY motif in the cytoplasmic juxtamembrane region (5). Two additional kinase deficient splice forms are expressed in colon cancer (6). The discoidin-like domain mediates binding to collagens I - V (1, 7, 8). DDR1 selectively recognizes the triple helical structure of collagen (7, 8). It is expressed on the cell surface as a dimer which can include different isoforms (5, 9). DDR1 oligomerization enhances collagen binding and also modulates collagen fibrillogenesis (10, 11). The transmembrane segment contains a leucine zipper and GxxxG motif, but neither is exclusively required for dimerization (9). Collagen binding induces prolonged autophosphorylation, including the NPxY motif (7, 8). Collagen binding also results in the proteolytic cleavage of a tyrosine phosphorylated 60 kDa C-terminal fragment (CTF), and a 60 kDa ECD fragment (12, 13). TIMP3 and TAPI-1 inhibit shedding of the ECD fragment but not the CTF (12). Overexpression of DDR1a promotes MMP-2 activation and results in an increased invasiveness of a glioblastoma cell line; DDR1b does not (14).

• References:

1. Vogel, W.F. et al. (2006) Cell. Signal. 18:1108.

2. Yoshimura, T. et al. (2005) Immunologic Res. 31:219.

3. Perez, J.L. et al. (1994) Oncogene 9:211.

4. Laval, S. et al. (1994) Cell Growth Differ. 5:1173.

5. Perez, J.L. et al. (1996) Oncogene 12:1469.

6. Alves, F. et al. (2001) FASEB J. 15:1321.

7. Shrivastava, A. et al. (1997) Mol. Cell 1:25.

8. Vogel, W. et al. (1997) Mol. Cell 1:13.

9. Nordeen, N.A. et al. (2006) J. Biol. Chem. 281:22744.

10. Leitinger, B. (2003) J. Biol. Chem. 278:16761.

11. Agarwal, G. et al. (2007) J. Mol. Biol. 367:443.

12. Slack, B.E. et al. (2006) J. Cell Biochem. 98:672.

13. Vogel, W.F. et al. (2001) FEBS Lett. 514:175.

14. Ram, R. et al. (2006) J. Neurooncol. 76:239.

• Long Name:

  Discoidin Domain Receptor 1

• Entrez Gene IDs:

  780 (Human)

• Alternate Names:

  CAK; CD167 antigen-like family member A; CD167a antigen; CD167a; DDR; DDR1; discoidin domain receptor family, member 1; discoidin domain receptor tyrosine kinase 1; Discoidin receptor tyrosine kinase; EC 2.7.10; EC 2.7.10.1; EDDR1; ENTRK4; Epithelial discoidin domain receptor 1; HGK2; MCK10; MCK-10; NTRK4; Protein-tyrosine kinase 3A; PTK3A protein tyrosine kinase 3A; PTK3A; receptor, type 4; RTK6; TRK E; TrkE