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Title Discoidin domain receptors in health and disease / Rafael Fridman, Paul H. Huang, editors.
Imprint New York : Springer, 2016.

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Subject Cell receptors.
Discoidin Domain Receptors -- physiology.
Receptors, Cell Surface.
Discoidin Domain Receptors -- therapeutic use.
Alt Name Fridman, Rafael,
Huang, Paul H.,
Description 1 online resource (xiv, 355 pages) : illustrations (some color)
polychrome rdacc
Note Includes index.
Online resource; title from PDF title page (SpringerLink, viewed August 19, 2016).
Summary The interactions of cells with their surrounding extracellular matrix (ECM) plays a pivotal role in driving normal cell behavior, from development to tissue differentiation and function. At the cellular level, organ homeostasis depends on a productive communication between cells and ECM, which eventually leads to the normal phenotypic repertoire that characterize each cell type in the organism. A failure to establish these normal interactions and to interpret the cues emanating from the ECM is one of the major causes in abnormal development and the pathogenesis of multiple diseases. To recognize and act upon the biophysical signals that are generated by the cross talk between cells and ECM, the cells developed specific receptors, among them a unique set of receptor tyrosine kinases (RTKs), known as the Discoidin Domain Receptors (DDRs). The DDRs are the only RTKs that specifically bind to and are activated by collagen, a major protein component of the ECM. Hence, the DDRs are part of the signaling networks that translate information from the ECM, and thus they are key regulators of cell-matrix interactions. Under physiological conditions, DDRs control cell and tissue homeostasis by acting on collagen sensors; transducing signals that regulate cell polarity, tissue morphogenesis, cell differentiation, and collagen deposition. DDRs play a key role in diseases that are characterized by dysfunction of the stromal component, which lead to abnormal collagen deposition and the resulting fibrotic response that disrupt normal organ function in disease of the cardiovascular system, lungs and kidneys, just to mention a few. In cancer, DDRs are hijacked by tumor and stromal cells to disrupt normal cell-collagen communication and initiate pro-oncogenic programs. Importantly, several cancer types exhibit DDR mutations, which are thought to alter receptor function, and contribute to cancer progression. Therefore, the strong causative association between altered RTK function and disease it is been translated today in the development of specific tyrosine kinase inhibitors targeting DDRs for various disease conditions. In spite of the accumulating evidence highlighting the importance of DDRs in health and diseases, there is still much to learn about these unique RTKs, as of today there is a lack in the medical literature of a book dedicated solely to DDRs. This is the first comprehensive volume dedicated to DDRs, which will fill a gap in the field and serve those interested in the scientific community to learn more about these important receptors in health and disease.
Bibliography Note Includes bibliographical references and index.
Contents Preface; Contents; Contributors; Part I: Discoidin Domain Receptor Biology and Roles in Physiology; Chapter 1: DDRs: Binding Properties, Cell Adhesion andModulation ofIntegrin Function; 1.1 Introduction; 1.2 DDR Binding Properties; 1.2.1 DDR Domain Organization; 1.2.2 Collagen Structure; 1.2.3 Ligand-Binding Specificity oftheDDRs; 1.2.4 DDR Binding Sites inCollagen; 1.2.5 Molecular Basis ofCollagen Binding; 1.3 DDR Functions inCell Adhesion andMigration; 1.4 Cooperation oftheDDRs withIntegrins; 1.5 Conclusions; References; Chapter 2: DDRs andCollagen Fibrillogenesis.
2.1 Introduction2.2 DDRs andCollagen Fibrillogenesis; 2.3 Fibrillogenesis ofCollagen Type I; 2.3.1 Collagen Biosynthesis; 2.3.2 Propeptide Cleavage; 2.3.3 Interaction ofDDRs withTropocollagen; 2.3.4 Collagen Microfibril; 2.3.5 Cell Surface; 2.3.6 Collagen Fibril; 2.3.7 Role ofGlycosylation; 2.3.8 Collagen Cross-Linking; 2.4 Functional Consequences; 2.4.1 Cell -- Matrix Interactions; 2.4.2 Matrix Mineralization; 2.4.3 Matrix Mechanics; 2.5 Other Collagen Types; 2.6 Conclusions; References; Chapter 3: DDR Structural Biology; 3.1 Introduction; 3.1.1 Structure oftheDS Domain.
3.1.2 Structure oftheDS-Like Domain3.1.3 Collagen Recognition oftheDS Domain; 3.1.4 Convergent Evolution ofGVMGFO-Binding Sites; 3.2 Transmembrane andIntracellular Domains; 3.3 Perspectives; References; Chapter 4: DDR Mouse Models; 4.1 Introduction; 4.2 Body Size; 4.2.1 DDR1-Deficient Mice; 4.2.2 DDR2-Deficient Mice; 4.2.3 Smallie: DDR2-Deficient Mutant Mice; 4.2.4 Dominant-Negative DDR2 Transgenic Mice; 4.2.5 DDR2-Overexpressing Transgenic Mice; 4.3 Reproduction; 4.3.1 Implantation inDDR1-Deficient Mice; 4.3.2 Mammary Glands inDDR1-Deficient Mice; 4.3.3 Ovaries inSmallie Mice.
4.3.4 Testes inSmallie Mice4.4 Skin Wound Healing; 4.5 Osteoarthritis; 4.5.1 Osteoarthritis inDDR2-Deficient Mice; 4.5.2 Osteoarthritis inDDR1-Deficient Mice; 4.6 Atherosclerosis; 4.7 Fibrosis; 4.7.1 Lung Fibrosis; 4.7.2 Kidney Fibrosis; 4.7.3 Liver Fibrosis; 4.8 Auditory Sensation; 4.9 Heart Structure andFunction; 4.10 Conclusion; References; Chapter 5: Discoidin Domain Receptors inInvertebrates; 5.1 Evolutionary Origin andDistribution ofDiscoidin Domain Receptors inInvertebrates; 5.2 Discoidin Domain Receptors inC. elegans; 5.2.1 The C. elegans Nervous System.
5.2.2 Discoidin Domain Receptor Expression inC. elegans5.2.3 C. elegans DDRs Function intheGuidance ofAxons AlongLongitudinal Nerve Tracts; 5.3 Collagens asPutative Ligands forDDRs inC. elegans; References; Part II: Discoidin Domain Receptors in Cancer; Chapter 6: Discoidin Domain Receptors andDisease; 6.1 DDRs andDevelopment; 6.2 DDRs andAtherosclerosis; 6.3 DDRs andArthritis; 6.4 DDRs andFibrosis; 6.5 DDRs andCancer; 6.5.1 DDRs Expression inCancer; 6.5.2 Tumor Cell Adhesion; 6.5.3 Tumor Cell Invasion andMigration.
ISBN 9781493963836 (electronic bk.)
149396383X (electronic bk.)
9781493963812 (print)
ISBN/ISSN 10.1007/978-1-4939-6383-6
OCLC # 956730974
Additional Format Printed edition: 9781493963812 (OCoLC)950952903.

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