Discoidin domain receptors: structural relations and functional implications.
Multicellular life relies on the presence of extracellular matrix to provide scaffolding for cells and tissue compartments. To provide communication between cells and tissues, a multitude of cell surface receptors are triggered by soluble ligands and components of the extracellular matrix. A large family of these receptors transmit signals through the use of an intrinsic tyrosine kinase function. The subgroup of discoidin domain receptors (DDRs) is distinguished from other members of the receptor tyrosine kinase family by a discoidin homology repeat in their extracellular domains that is also found in a variety of other transmembrane and secreted proteins. Sequence comparisons show that non-mammalian orthologs of DDRs exist: three closely related genes in Caenorhabditis and one in the sponge Geodia cydonium. Recently, various types of collagen have been identified as the ligands for the two mammalian discoidin domain receptor tyrosine kinases, DDR1 and DDR2. The binding of collagen to DDRs results in a delayed but sustained tyrosine kinase activation. Both receptors display several potential tyrosine phosphorylation sites that are able to relay the signal by interacting with cytoplasmic effector proteins. The potential cross-talk to other receptors for collagen and the clinical aspects of DDR function are discussed.
Vogel
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Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. vogel@mshri.on.ca
D000818:Animals; D003094:Collagen / Q000378:metabolism; D000070818:Discoidin Domain Receptors; D015870:Gene Expression; D006801:Humans; D020794:Receptor Protein-Tyrosine Kinases; D011975:Receptors, Mitogen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D011975:Receptors, Mitogen; D003094:Collagen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases