Recombinant Human Epithelial discoidin domain-containing receptor 1 (DDR1), partial (Active)

Function

Tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and MMP9, and thereby facilitates cell migration and wound healing. Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing (By similarity). Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing. Also plays a role in tumor cell invasion. Phosphorylates PTPN11

Subcellular Location

Cell membrane (Single-pass type I membrane protein)

Tissue Specificity

Detected in T-47D, MDA-MB-175 and HBL-100 breast carcinoma cells, A-431 epidermoid carcinoma cells, SW48 and SNU-C2B colon carcinoma cells and Hs 294T melanoma cells (at protein level). Expressed at low levels in most adult tissues and is highest in the brain, lung, placenta and kidney. Lower levels of expression are detected in melanocytes, heart, liver, skeletal muscle and pancreas. Abundant in breast carcinoma cell lines. In the colonic mucosa, expressed in epithelia but not in the connective tissue of the lamina propria. In the thyroid gland, expressed in the epithelium of the thyroid follicles. In pancreas, expressed in the islets of Langerhans cells, but not in the surrounding epithelial cells of the exocrine pancreas. In kidney, expressed in the epithelia of the distal tubules. Not expressed in connective tissue, endothelial cells, adipose tissue, muscle cells or cells of hematopoietic origin

Subunit

Homodimer. Interacts (via PPxY motif) with WWC1 (via WW domains) in a collagen-regulated manner. Forms a tripartite complex with WWC1 and PRKCZ, but predominantly in the absence of collagen. Interacts (tyrosine phosphorylated) with SHC1. Interacts with SRC. Interacts with MYH9. Interacts with CDH1. Interacts with PTPN11. Interacts with NCK2

• di Marco E. et al. Molecular cloning of trkE, a novel trk-related putative tyrosine kinase receptor isolated from normal human keratinocytes and widely expressed by normal human tissues. — J. Biol. Chem. (1993)
• Johnson J.D. et al. A receptor tyrosine kinase found in breast carcinoma cells has an extracellular discoidin I-like domain. — Proc. Natl. Acad. Sci. U.S.A. (1993)
• Laval S. et al. Isolation and characterization of an epithelial-specific receptor tyrosine kinase from an ovarian cancer cell line. — Cell Growth Differ. (1994)
• Perez J.L. et al. Identification and chromosomal mapping of a receptor tyrosine kinase with a putative phospholipid binding sequence in its ectodomain. — Oncogene (1994)
• Sakuma S. et al. Receptor protein tyrosine kinase DDR is up-regulated by p53 protein. — FEBS Lett. (1996)
• Playford M.P. et al. The genomic structure of discoidin receptor tyrosine kinase. — Genome Res. (1996)
• Perez J.L. et al. Identification of two isoforms of the Cak receptor kinase that are coexpressed in breast tumor cell lines. — Oncogene (1996)
• Jin P. et al. Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. — Arthritis Res. Ther. (2008)