Download Discoidin Domain Receptors in Health and Disease by Rafael Fridman, Paul H. Huang PDF

By Rafael Fridman, Paul H. Huang

The interactions of cells with their surrounding extracellular matrix (ECM) performs a pivotal function in riding general cellphone habit, from improvement to tissue differentiation and serve as. on the mobile point, organ homeostasis will depend on a effective communique among cells and ECM, which finally ends up in the conventional phenotypic repertoire that signify each one mobilephone style within the organism. A failure to set up those basic interactions and to interpret the cues emanating from the ECM is likely one of the significant motives in irregular improvement and the pathogenesis of a number of illnesses. to acknowledge and act upon the biophysical indications which are generated by means of the move speak among cells and ECM, the cells constructed particular receptors, between them a distinct set of receptor tyrosine kinases (RTKs), referred to as the Discoidin area Receptors (DDRs). The DDRs are the one RTKs that particularly bind to and are activated by means of collagen, an enormous protein portion of the ECM. accordingly, the DDRs are a part of the signaling networks that translate details from the ECM, and hence they're key regulators of cell-matrix interactions. lower than physiological stipulations, DDRs keep watch over telephone and tissue homeostasis through performing on collagen sensors; transducing signs that keep an eye on phone polarity, tissue morphogenesis, mobile differentiation, and collagen deposition. DDRs play a key position in illnesses which are characterised by way of disorder of the stromal part, which result in irregular collagen deposition and the ensuing fibrotic reaction that disrupt basic organ functionality in ailment of the cardiovascular approach, lungs and kidneys, simply to point out a number of. In melanoma, DDRs are hijacked through tumor and stromal cells to disrupt general cell-collagen conversation and begin pro-oncogenic courses. Importantly, a number of melanoma forms show DDR mutations, that are idea to change receptor functionality, and give a contribution to melanoma development. for that reason, the powerful causative organization among altered RTK functionality and sickness it truly is been translated this present day within the improvement of particular tyrosine kinase inhibitors concentrating on DDRs for numerous sickness stipulations. regardless of the collecting proof highlighting the significance of DDRs in health and wellbeing and ailments, there's nonetheless a lot to benefit approximately those designated RTKs, as of this present day there's a lack within the scientific literature of a e-book committed completely to DDRs. this is often the 1st entire quantity devoted to DDRs, with the intention to fill a spot within the box and serve these attracted to the medical group to benefit extra approximately those vital receptors in health and wellbeing and disease.

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Adv Protein Chem 70:301–339 13. Myllyharju J, Kivirikko KI (2004) Collagens, modifying enzymes and their mutations in humans, flies and worms. Trends Genet 20(1):33–43 14. Leitinger B (2011) Transmembrane collagen receptors. Annu Rev Cell Dev Biol 27:265–290. 1146/annurev-cellbio-092910-154013 15. Agarwal G, Kovac L, Radziejewski C, Samuelsson SJ (2002) Binding of discoidin domain receptor 2 to collagen I: an atomic force microscopy investigation. Biochemistry 41(37):11091–11098 16. Leitinger B (2003) Molecular analysis of collagen binding by the human discoidin domain receptors, DDR1 and DDR2.

Bipolar fibrils can further elongate from both their N-terminus ends by addition of monomers. Fibril length has been estimated to be 20–40 μm in the developing tissue and in the mm range for the adult tissue [107]. 38 G. Agarwal In vivo, the lateral growth of the collagen fibril is controlled by the binding of small leucine-rich proteoglycans (SLRPs) as well as other CBPs (Fig. 3) [108]. In the cornea, small diameter fibrils with constant interfibrillar spacing are associated with a high keratan sulfate proteoglycan (KSPG) content, while the larger diameter fibrils in the sclera are characterized by an absence of KSPG and presence of chondroitin sulfate (CSPG), dermatan sulfate (DSPG), and hyaluronic acid [109].

431528 55. Higashiyama S, Nanba D, Nakayama H, Inoue H, Fukuda S (2011) Ectodomain shedding and remnant peptide signalling of EGFRs and their ligands. J Biochem 150(1):15–22. 1093/ jb/mvr068 56. Yoshida D, Teramoto A (2007) Enhancement of pituitary adenoma cell invasion and adhesion is mediated by discoidin domain receptor-1. J Neurooncol 82:29–40 20 B. Leitinger 57. Ram R, Lorente G, Nikolich K, Urfer R, Foehr E, Nagavarapu U (2006) Discoidin domain receptor-1a (DDR1a) promotes glioma cell invasion and adhesion in association with matrix metalloproteinase-2.

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