Vogel Wolfgang F, Abdulhussein Rahim, Ford Caroline E
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario Canada, M5S 1A8.
Cell Signal. 2006 Aug;18(8):1108-16. doi: 10.1016/j.cellsig.2006.02.012. Epub 2006 Feb 28.
Discoidin Domain Receptors (DDRs) have recently emerged as non-integrin-type receptors for collagen. The two mammalian gene products Discoidin Domain Receptor 1 and -2 constitute a subfamily of tyrosine kinase receptors that are selectively expressed in a number of different cell types and organs. Upon collagen activation, DDRs regulate cell adhesion, proliferation and extracellular matrix remodeling. Here we review the various signaling pathways and cellular responses evoked by activated DDRs. Additionally, we give an overview of the more recent advances in understanding the role of DDRs in various human diseases, in particular during tumor progression, atherosclerosis, inflammation and tissue fibrosis. Furthermore, we discuss potential roles of genes homologous to mammalian DDRs identified in flies, worms and sponges. We show that the structural organization of these DDR-related genes is highly conserved throughout evolution suggesting that invertebrate DDRs may also function as receptors for collagen. By highlighting current questions about these unusual collagen receptors, we hope to attract new research on DDRs from a variety of different fields.
盘状结构域受体（DDRs）最近已成为胶原蛋白的非整合素型受体。两种哺乳动物基因产物盘状结构域受体1和-2构成了酪氨酸激酶受体亚家族，它们在多种不同细胞类型和器官中选择性表达。在胶原蛋白激活后，DDRs调节细胞粘附、增殖和细胞外基质重塑。在这里，我们综述了激活的DDRs引发的各种信号通路和细胞反应。此外，我们概述了在理解DDRs在各种人类疾病中的作用方面的最新进展，特别是在肿瘤进展、动脉粥样硬化、炎症和组织纤维化过程中。此外，我们讨论了在果蝇、蠕虫和海绵中鉴定出的与哺乳动物DDRs同源的基因的潜在作用。我们表明，这些与DDR相关的基因的结构组织在整个进化过程中高度保守，这表明无脊椎动物的DDRs也可能作为胶原蛋白的受体发挥作用。通过强调关于这些不寻常的胶原蛋白受体的当前问题，我们希望吸引来自各种不同领域的关于DDRs的新研究。
