Vogel W
Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
FASEB J. 1999;13 Suppl:S77-82. doi: 10.1096/fasebj.13.9001.s77.
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.
多细胞生物依赖细胞外基质的存在为细胞和组织区室提供支架。为了实现细胞与组织之间的通讯，众多细胞表面受体可被可溶性配体和细胞外基质成分激活。这些受体中的一大类通过内在的酪氨酸激酶功能来传递信号。盘状结构域受体（DDR）亚组与受体酪氨酸激酶家族的其他成员不同，其细胞外结构域含有盘状同源重复序列，该序列也存在于多种其他跨膜蛋白和分泌蛋白中。序列比较表明，DDR存在非哺乳动物直系同源物：秀丽隐杆线虫中有三个密切相关的基因，海绵地穴海绵中有一个。最近，已鉴定出多种类型的胶原蛋白是两种哺乳动物盘状结构域受体酪氨酸激酶DDR1和DDR2的配体。胶原蛋白与DDR的结合导致酪氨酸激酶延迟但持续激活。两种受体都显示出几个潜在的酪氨酸磷酸化位点，这些位点能够通过与细胞质效应蛋白相互作用来传递信号。本文还讨论了DDR与其他胶原蛋白受体之间潜在的相互作用以及DDR功能的临床意义。
