Cell Surface Proteases
Cell Surface Proteases

Author:

Publisher: Elsevier

Published: 2003-05-03

Total Pages: 475

ISBN-13: 0080490883

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Cell Surface Proteases provides a comprehensive overview of these important enzymes that catalyze the hydrolysis of a protein as it degrades to a simpler substance. In the 1990s, an explosion of new discoveries shed light on the role of cell surface proteases and extended it beyond degradation of extracellular matrix components to include its influence on growth factors, cell signaling, and other cellular events. This volume unites the scientific literature from across disciplines and teases out unified themes of interactions between cell surface proteases and interconnecting cell surface-related systems -- including integrins and other adhesion molecules. Scientists and students involved in developmental biology, cell biology and disease processes will find this an indispensable resource.* Provides an overview of the entire field of cell surface proteases in a single volume* Presents major issues and astonishing discoveries at the forefront of modern developmental biology and developmental medicine * A thematic volume in the longest-running forum for contemporary issues in developmental biology with over 30 years of coverage

Activation of Viruses by Host Proteases
Activation of Viruses by Host Proteases

Author: Eva Böttcher-Friebertshäuser

Publisher: Springer

Published: 2018-05-22

Total Pages: 337

ISBN-13: 3319754742

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This book will give an overview on viruses undergoing proteolytic activation through host proteases. The chapters will be organized in three themed parts, the first part describing respective viruses and their characteristics in detail. In the second part the molecular and cellular biology of the proteases involved as well as their physiological functions will be further explored. The third part will contain a chapter on protease inhibitors that are promising tools for antiviral therapy. This book will engage scholars in virology and medical microbiology as well as researchers with an interest in enzymology and protein structure and function relationship.

Proteases: Structure and Function
Proteases: Structure and Function

Author: Klaudia Brix

Publisher: Springer Science & Business Media

Published: 2014-01-21

Total Pages: 568

ISBN-13: 3709108853

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Proteolysis is an irreversible posttranslational modification affecting each and every protein from its biosynthesis to its degradation. Limited proteolysis regulates targeting and activity throughout the lifetime of proteins. Balancing proteolysis is therefore crucial for physiological homeostasis. Control mechanisms include proteolytic maturation of zymogens resulting in active proteases and the shut down of proteolysis by counteracting endogenous protease inhibitors. Beyond the protein level, proteolytic enzymes are involved in key decisions during development that determine life and death – from single cells to adult individuals. In particular, we are becoming aware of the subtle role that proteases play in signaling events within proteolysis networks, in which the enzymes act synergistically and form alliances in a web-like fashion. Proteases come in different flavors. At least five families of mechanistically distinct enzymes and even more inhibitor families are known to date, many family members are still to be studied in detail. We have learned a lot about the diversity of the about 600 proteases in the human genome and begin to understand their physiological roles in the degradome. However, there are still many open questions regarding their actions in pathophysiology. It is in this area where the development of small molecule inhibitors as therapeutic agents is extremely promising. Approaching proteolysis as the most important, irreversible post-translational protein modification essentially requires an integrated effort of complementary research disciplines. In fact, proteolytic enzymes seem as diverse as the scientists working with these intriguing proteins. This book reflects the efforts of many in this exciting field of research where team and network formations are essential to move ahead.

Extracellular Targeting of Cell Signaling in Cancer
Extracellular Targeting of Cell Signaling in Cancer

Author: James W. Janetka

Publisher: John Wiley & Sons

Published: 2018-07-23

Total Pages: 482

ISBN-13: 1119300185

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International experts present innovative therapeutic strategies to treat cancer patients and prevent disease progression Extracellular Targeting of Cell Signaling in Cancer highlights innovative therapeutic strategies to treat cancer metastasis and prevent tumor progression. Currently, there are no drugs available to treat or prevent metastatic cancer other than non-selective, toxic chemotherapy. With contributions from an international panel of experts in the field, the book integrates diverse aspects of biochemistry, molecular biology, protein engineering, proteomics, cell biology, pharmacology, biophysics, structural biology, medicinal chemistry and drug development. A large class of proteins called kinases are enzymes required by cancer cells to grow, proliferate, and survive apoptosis (death) by the immune system. Two important kinases are MET and RON which are receptor tyrosine kinases (RTKs) that initiate cell signaling pathways outside the cell surface in response to extracellular ligands (growth factors.) Both kinases are oncogenes which are required by cancer cells to migrate away from the primary tumor, invade surrounding tissue and metastasize. MET and RON reside on both cancer cells and the support cells surrounding the tumor, called the microenvironment. MET and RON are activated by their particular ligands, the growth factors HGF and MSP, respectively. Blocking MET and RON kinase activation and downstream signaling is a promising therapeutic strategy for preventing tumor progression and metastasis. Written for cancer physicians and biologists as well as drug discovery and development teams in both industry and academia, this is the first book of its kind which explores novel approaches to inhibit MET and RON kinases other than traditional small molecule kinase inhibitors. These new strategies target key tumorigenic processes on the outside of the cell, such as growth factor activation by proteases. These unique strategies have promising potential as an improved alternative to kinase inhibitors, chemotherapy, or radiation treatment.

Monitoring Proteolytic Cleavage of a Membrane Metalloproteinase on the Cell Surface with a Cell-based Assay
Monitoring Proteolytic Cleavage of a Membrane Metalloproteinase on the Cell Surface with a Cell-based Assay

Author:

Publisher:

Published: 2016

Total Pages: 44

ISBN-13:

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Proteolysis is one of the most essential biological processes as it serves different purposes such as protein maturation, degradation, and regulation. Proteolysis at the cell surface and extracellular matrix (ECM) plays significant roles in the progression of certain diseases as exemplified by the role of Matrix Metalloproteinase 14 (MMP-14) in cancer. MMP-14 is a ubiquitously-expressed cell surface protease known to activate several soluble MMPs (EC-MMPs) via extracellular proteolysis. Active EC-MMPs are then used for the restructuring of the ECM that can facilitate cell migration and development. MMP-14 is known to be highly expressed in cancer tissues, as cells require constant remodeling of the ECM to accommodate fast replication and migration that leads to metastasis. The aim of this research is to develop a novel cell-based assay for the monitoring of proteolytic cleavage on the cell surface. We propose to develop such assay using MMP-14 cleavage activity as a proof-of-principle. The assay could also serve as a screening tool for the search of novel MMP-14 inhibitors. The assay is based on a two-tag system flanking an optimized substrate of MMP-14 that serves as the primary detection element that can distinguish cleavage and non-cleavage events. A fluorescent protein is later introduced as a visual marker for cell surface localization by fluorescence microscopy. Lastly, the entire scaffold protein will be targeted and anchored on the cell surface by the addition of the C-terminal transmembrane domain of mouse Lyt-2 cell surface protein. The utility of the assay for monitoring cleavage on the cell surface will be demonstrated with the overexpression of MMP-14 as a proof-of-principle. Once the assay is calibrated and optimized to function as intended, it could also be further used as a platform to monitor other biologically important surface proteolysis events such as cleavage of the Amyloid Precursor Protein (APP) in Alzheimer disease and proteolysis of sialic acid by the influenza virus neuraminidase (NA) for the spread of viral particles. More importantly, it can also be adapted to a high-throughput screening (HTS) platform for the screening for novel inhibitors of those aforementioned proteases.

TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades
TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades

Author: Wolfgang B. Liedtke, MD, PH.D.

Publisher: CRC Press

Published: 2006-09-29

Total Pages: 502

ISBN-13: 1420005847

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Since the first TRP ion channel was discovered in Drosophila melanogaster in 1989, the progress made in this area of signaling research has yielded findings that offer the potential to dramatically impact human health and wellness. Involved in gateway activity for all five of our senses, TRP channels have been shown to respond to a wide range of st

Essentials of Glycobiology
Essentials of Glycobiology

Author: Ajit Varki

Publisher: CSHL Press

Published: 1999

Total Pages: 694

ISBN-13: 9780879696818

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Sugar chains (glycans) are often attached to proteins and lipids and have multiple roles in the organization and function of all organisms. "Essentials of Glycobiology" describes their biogenesis and function and offers a useful gateway to the understanding of glycans.

Cell Surface Peptidases in Health and Disease
Cell Surface Peptidases in Health and Disease

Author: A.J. Kenny

Publisher: Taylor & Francis

Published: 1997-07

Total Pages: 408

ISBN-13:

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Cells bristle with a battery of surface enzymes, of which the peptidases form the largest and best studied group. These ectopeptidases play crucial roles in many diverse biological functions, including the termination of peptide signals in the nervous system and at peripheral sites. Some of their key physiological roles, such as those of angiotensin- and endothelin-converting enzymes in generating vasoconstrictive agents and endopeptidase-24.11 in activating natriuretic peptides, enkephalins and tachykinins, have made them prime targets for the pharmaceutical industry. Interest among immunologists and haematologists was aroused when several were shown to be identical to cell-surface markers (CD antigens) on human leukocytes. Virologists have been excited to find that some double as receptors for certain viruses.