Human DDR1 Antibody

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. 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. 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. Compared to isoform DDR1b, DDR1a lacks 37 aa’s that include a Shc-interacting NPxY motif in the cytoplasmic juxtamembrane region. Two additional kinase deficient splice forms are expressed in colon cancer. The discoidin-like domain mediates binding to collagens I-V. DDR1 selectively recognizes the triple helical structure of collagen. It is expressed on the cell surface as a dimer which can include different isoforms. DDR1 oligomerization enhances collagen binding and also modulates collagen fibrillogenesis. The transmembrane segment contains a leucine zipper and GxxxG motif, but neither is exclusively required for dimerization. Collagen binding induces prolonged autophosphorylation, including the NPxY motif. Collagen binding also results in the proteolytic cleavage of a tyrosine phosphorylated 60 kDa C-terminal fragment (CTF), and a 60 kDa ECD fragment. TIMP3 and TAPI-1 inhibit shedding of the ECD fragment but not the CTF. Over-expression of DDR1a promotes MMP-2 activation and results in an increased invasiveness of a glioblastoma cell line; DDR1b does not.