Analysis of TGF-[beta] Signaling Receptors PDF Download

Author: Frances Weis-Garcia
Publisher:
ISBN:
Category :
Languages : en
Pages : 350

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Author: Jolanta Barańska
Publisher: Springer Nature
ISBN: 3030306518
Category : Medical
Languages : en
Pages : 311

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Gliomas, developing in the brain from the transformed glial cells, are a very special kind of tumor, extremely refractory to conventional treatments. Therefore, for the development of new antitumor strategies, a better understanding of molecular mechanisms responsible for their biology, growth and invasion is still needed. This book is a reference on cellular signaling processes regulating gliomas physiology and invasiveness. The work is focused on the mechanism of nucleotide receptor activation by exogenous nucleotides and formation of complex signaling cascades induced by growth factors, cytokines and cannabinoids. The second edition of the book enriched in new chapters provides a framework explaining how signal transduction elements may modulate numerous genetic and epigenetic alterations, describes the role of local microenvironment in cellular growth, progression and invasion and, in the light of extensive new results, presents perspectives concerning potential targets for gliomas therapy.

Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

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The principal goal of this project is to understand the transforming growth factor-Beta (TGF Beta) receptor signal transduction pathways and the molecular mechanism underlying the regulation of the activity of the TOFQ receptor kinases. TGF Beta could suppress the growth of breast cancer cells both in vivo and in vitro (1, 2, 3), and this function requires the expression of functional TGF Beta receptors (2, 3) and downstream signaling molecules (4). The TGF Beta family of cytokines has a wide range of biological functions including tumor suppression, extracellular matrix production, embryonic development, and regulation of differentiation(5). These functions are mediated by three specific surface receptors, Types I, II and III, all of which have been cloned (6, 7, 8, 9). The types I and II receptors for TGF Beta, T BetaRI and T BetaRll, are members of the first known receptor serine/threonine kinase family, and share 40% homology between their kinase domains. T BetaRll contains an extracellular domain which binds TGF beta, a transmembrane domain and a cytoplasmic domain with serine/threonine kinase activity. T BetaRI also has an extracellular domain even though it does not bind TGF Beta when expressed without T BetaRII. The cytoplasmic portion of T BetaRI contains a kinase domain and a membrane proximal region which contains a Oly-Ser rich sequence (OS box) that has been proposed to be important for the activation of T BetaRI (10). Both receptors exist normally as homodimers on the cell surface (11, 12) and their kinase activities are essential for signal transduction (6, 8, 9, 13). Binding of TGF Beta1 to T BetaRII induces the formation of a heteromeric complex of T BetaRI and T BetaRll (6, 8, 9, 13), which results in transphosphorylation of T BetaRI by the constitutively active TJ3Rll.

Author: Rik Derynck
Publisher: CSHL Press
ISBN: 0879697520
Category : Transforming growth factors-beta
Languages : en
Pages : 1108

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Transforming growth factor-[beta] (TGF-[beta]), identified nearly three decades ago, is a secreted polypeptide that functions in critical cell cycle processes, including cellular proliferation, differentiation, and development: It belongs to a large protein family that, in humans, contains 33 members, including activins, inhibins, bone morphogenetic proteins, growth and differentiation factors, and Mullerian inhibiting substance. This volume draws on the world's leading laboratories to comprehensively cover all aspects of the biology of TGF-[beta] and related factors. In addition to providing historical and background information, it describes the cell biology and signaling pathways of TGF-[beta] members in detail, including the roles of TGF-[beta] factors in the development and physiology of humans and model organisms. The last few chapters are devoted to the role of TGF-[beta] members in cancer and other diseases, as well as the possibilities for therapeutics based on knowledge of signaling pathways and macromolecular structures. It serves as a comprehensive reference work for both specialists and researchers less familiar with the field.

Author: Manfred Schwab
Publisher: Springer Science & Business Media
ISBN: 3540368477
Category : Medical
Languages : en
Pages : 3307

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This comprehensive encyclopedic reference provides rapid access to focused information on topics of cancer research for clinicians, research scientists and advanced students. Given the overwhelming success of the first edition, which appeared in 2001, and fast development in the different fields of cancer research, it has been decided to publish a second fully revised and expanded edition. With an A-Z format of over 7,000 entries, more than 1,000 contributing authors provide a complete reference to cancer. The merging of different basic and clinical scientific disciplines towards the common goal of fighting cancer makes such a comprehensive reference source all the more timely.

Author: Peter Dijke
Publisher: Springer Science & Business Media
ISBN: 1402047096
Category : Science
Languages : en
Pages : 489

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This is the first comprehensive book on Smad signal transduction. Forward looking reviews of Smads are provided in a series of 22 cutting-edge chapters. The book is written for an audience with basic understanding of molecular and cell biology. This volume provides an in-depth review of a rapidly developing field and extensive cross-references between chapters are provided.

Author: Robert C. Bast, Jr.
Publisher: John Wiley & Sons
ISBN: 111900084X
Category : Medical
Languages : en
Pages : 2004

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Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates

Author: Dan Simionescu
Publisher: BoD – Books on Demand
ISBN: 9535130234
Category : Medical
Languages : en
Pages : 466

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The purpose of this book is to highlight novel advances in the field and to incentivize scientists from a variety of fields to pursue angiogenesis as a research avenue. Blood vessel formation and maturation to capillaries, arteries, or veins is a fascinating area which can appeal to multiple scientists, students, and professors alike. Angiogenesis is relevant to medicine, engineering, pharmacology, and pathology and to the many patients suffering from blood vessel diseases and cancer, among others. We are hoping that this book will become a source of inspiration and novel ideas for all.

Author: Gerhard Krauss
Publisher: John Wiley & Sons
ISBN: 3527605762
Category : Science
Languages : de
Pages : 558

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This all-new edition of a classic text has been thoroughly revised to keep pace with the rapid progress in signal transduction research. With didactic skill and clarity the author relates the observed biological phenomena to the underlying biochemical processes. Directed to advanced students, teachers, and researchers in biochemistry and molecular biology, this book describes the molecular basis of signal transduction, regulated gene expression, the cell cycle, tumorigenesis and apoptosis. "Provides a comprehensive account of cell signaling and signal transduction and, where possible, explains these processes at the molecular level" (Angewandte Chemie) "The clear and didactic presentation makes it a textbook very useful for students and researchers not familiar with all aspects of cell regulation." (Biochemistry) "This book is actually two books: Regulation and Signal Transduction." (Drug Research)

Author: Carter Li
Publisher:
ISBN:
Category :
Languages : en
Pages :

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"Transforming Growth Factor [beta] (TGF-[beta]) is a multifunctional growth factor involved in a wide variety of cellular processes. Expressed in a majority of mammalian cells, TGF-[beta] has been shown to play pivotal roles in immunoregulation, cellular homeostasis, apoptosis, and embryonic development. Perturbations in the TGF-[beta] signaling pathway results in extensive vascular, neural, and osteal developmental defects, and massive autoimmune inflammatory responses. TGF-[beta] signals through a pair of transmembrane serine/threonine kinases known as type I (T[beta]RI) and type II TGF-[beta] (T[beta]RII) signaling receptors. The TGF-[beta] ligand binds to T[beta]RII, which transphosphorylates the T[beta]RI receptor, initiating an intracellular phosphorylation cascade where the activated T[beta]RI phosphorylates receptor-regulated Smads (R-Smads) which subsequently bind common-mediator Smads (Co-Smads) forming R-Smad/Co-Smad complexes. The R-Smad/Co-Smad complexes then translocate into the nucleus to regulate gene expression through interactions with transcription factors, co-activators and co-repressors. In addition to the T[beta]RI and T[beta]RII signaling receptors, many cell types express TGF-[beta] co-receptors known as betaglycan and endoglin that bind TGF-[beta] and modulate TGF-[beta] signaling in a cell-specific manner. Our research group has previously identified CD109, a GPI-anchored protein, as a novel TGF-[beta] co-receptor. CD109 binds TGF-[beta] to form a heteromeric complex with the TGF-[beta] signaling receptors and inhibits TGF-[beta] signaling through caveolae-mediated TGF-[beta] receptor internalization and degradation. Furthermore, our group has demonstrated that endogenous CD109 can be released from the cell surface by endogenous PIPLC enzymes and subsequently bind TGF-[beta] with high affinity. Aberrant TGF-[beta] signaling plays a central role in a variety of pathologies. Strategies for regulating aberrant TGF-[beta] action by diminishing TGF-[beta] access to its receptors include development of neutralizing anti-TGF-[beta] antibodies and TGF-[beta] ligand traps. Characterizations of receptor-ligand interactions have demonstrated the potential of receptor ectodomain-based ligand traps to sequester TGF-[beta] and inhibit TGF-[beta] signaling. As CD109 and alpha-2-macroglobulin ([alpha]2m) belong to the same family of thioester containing proteins, I set out to determine if soluble CD109 can act as a TGF-[beta] antagonist. As CD109 and [alpha]2m share similar structural homologies, I set out to determine the putative TGF-[beta] binding domain of CD109. In my findings, I established that soluble CD109 acts as a TGF-[beta] antagonist, by demonstrating the ability of recombinant soluble CD109 protein to bind all three mammalian TGF-[beta] isoforms and negatively modulate TGF-[beta] signaling and TGF-[beta]-induced cellular responses. Furthermore, based on my sequence homology analysis, I predict that the putative TGF-[beta] binding domain of CD109 to encompass amino acids 687-711, which includes a WIW hydrophobic sequence and acidic residues thought to confer TGF-[beta] binding functionality similar to that of T[beta]RII and [alpha]2m. Moreover, I have generated CD109 derived peptides based on the putative binding domain of the CD109 protein and CD109 site-directed mutants to determine the TGF-[beta] binding domain of CD109. My results indicate that peptides derived from the putative binding domain of TGF-[beta] (CD109 amino acid 687-711) can bind all three mammalian TGF-[beta] isoforms, modulate TGF-[beta] signaling and TGF-[beta]-induced cellular responses, and that CD109 site-directed mutants can abrogate CD109 inhibition of TGF-[beta] induced transcriptional activity. Collectively, these findings suggest that soluble CD109 plays an important role in negatively regulating TGF-[beta] signaling and that a putative TGF-[beta] putative binding region of CD109 is at least partially responsible for binding TGF-[beta] and antagonizing TGF-[beta] signaling and responses.In addition to unravelling a potential mechanism by which TGF-[beta] action is regulated by CD109 in vivo, the above findings have important implications in TGF-[beta]-related diseases." --