Transforming Growth Factor-beta (TGF-β) -related Signal Transduction in Drosophila Melanogaster PDF Download

Author: Karen Staehling-Hampton
Publisher:
ISBN:
Category :
Languages : en
Pages : 400

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Author: John B. Hudson
Publisher:
ISBN:
Category : Drosophila
Languages : en
Pages : 258

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Author: Yijing Chen
Publisher:
ISBN:
Category :
Languages : en
Pages : 364

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

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Book Description
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: F. Hoffman
Publisher:
ISBN:
Category :
Languages : en
Pages : 74

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The transforming growth factor beta (TGF-Beta) superfamily consists of a growing number of identified growth factors regulating remarkably diverse aspects of cell life, including cell growth, differentiation, death, adhesion and migration.

Author: Janine C. Quijano
Publisher:
ISBN:
Category : Cellular signal transduction
Languages : en
Pages : 184

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Proper cell growth and differentiation requires the integration of multiple signaling pathways that are maintained by various post-translational modifications. Many proteins in signal transduction pathways are conserved between humans and model organisms. My dissertation characterizes four previously unknown manners of regulation in the Drosophila Decapentaplegic (Dpp) pathway, a pathway within TGF-beta family. First, I present data that the Dpp signal transducer, Mothers Against Dpp (Mad), is phosphorylated by Zeste-white 3 (Zw3), a kinase involved in the Wingless pathway. This phosphorylation event occurs independently of canonical phosphorylation of Mad by the Dpp receptor. Using ectopic expression of different alleles of Mad, I show that Zw3 phosphorylation of Mad occurs during the cell cycle in pro-neuronal cells and the loss of phosphorylation of Mad by Zw3 results in ectopic neuronal cells. Thus, Mad phosphorylation by Zw3 is necessary for cell cycle control in pro-neuronal cells. Second, I have shown that the regulator dSno, which has previously been shown to be a TGF-beta antagonist and agonist, is also a Wingless pathway antagonist. Loss of function flip-out clones and ectopic expression of dSno both resulted in changes of Wingless signaling. Further analysis revealed that dSno acts at or below the level of Armadillo (Arm) to inhibit target gene expression. Third, I have demonstrated that the protein Bonus, which is known to be involved in chromatin modification, is required in dorsal-ventral patterning. Further experiments discovered that the chromatin modifier is not only a necessary Dpp agonist, but it is also necessary for nuclear localization of Dorsal during Toll signaling. Last, I showed that longitudinal lacking-like (lola-like) is also required in dorsal-ventral patterning. The loss of maternally expressed lola-like prevents dpp transcription. This shows that lola-like is integral in the Dpp pathway. The study of these four proteins integrates different signaling pathways, demonstrating that the process of development is a web of connections rather than a linear pathway.

Author: Audrey Mei-Fen Huang
Publisher:
ISBN:
Category :
Languages : en
Pages : 396

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Author: Yi Arial Zeng
Publisher:
ISBN:
Category : Cellular signal transduction
Languages : en
Pages : 0

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The development of muticellular organisms requires precisely regulated cell-cell communication mediated by numerous signal transduction pathways. Regulatory "crosstalk" is essential in integrating the many inputs and stimuli that each cell receives, and ensuring that a cell responds appropriately. Drosophila nemo (nmo) is the founding member of an evolutionarily conserved family of serirdthreonine protein kinases kinases that are involved in several Wnt signal transduction pathways. Consistent with these findings, the detailed genetic analyses of the role of Nemo in Drosophila wing development support the proposed antagonistic role for Nemo in Drosophila Wingless (Wg) signaling pathway. In addition, I provide evidence that transcription of nmo is induced by high levels of Wg signaling in the developing wing disc. Our results indicate that Nemo acts as an intracellular feedback inhibitor of Wg during wing development and that it is a novel Wg target gene. In this study, a novel function for Nemo in inhibition of Drosophila Bone Morphogenetic Protein (BMP) signalling is also revealed. Genetic interaction studies demonstrate that nmo can antagonize BMP signaling and can inhibit the expression of BMP dependent target genes during wing development. Nemo can bind to and phosphorylate the BMP effectors Mad and Medea. In cell culture, phosphorylation by Nemo blocks the nuclear translocation of Mad. Mutation of a single Nemo phosphorylation site in Mad relieves the inhibition of nuclear translocation, and causes ligand-independent nuclear translocation. This is the first example of inhibition of Drosophila BMP signaling by a MAPK and also represents an original mechanism of Smad inhibition through phosphorylation of a conserved Serine residue within the MHI domain of Mad. In Drosophila wing imaginal disc development, Wg signalling pathway organizes the dorsal-ventral (DV) axis, while BMP signaling pathway is required to pattern the anterior-posterior (AP) axis. In the analyses of the roles of Nemo in Wg and BMP signaling pathways, a novel crosstalk between Wg and Dpp signaling is unveiled, in which Wg-dependent gene expression is suppressed by ectopic Dpp signaling. In addition, Arm and Mad compete for the binding of dTCF in cell culture. Consistently, in vivo, supplement of dTCF is able to rescue the suppression of Wg-dependent gene expression caused by ectopic Mad. Our results suggest a novel mechanism that Dpp represses Wg target gene by influencing the binding of Arm and dTCF.

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

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Book Description
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: Jane Young Cho
Publisher:
ISBN: 9781124521800
Category :
Languages : en
Pages : 206

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ABSTRACT OF THE DISSERTATION The evolutionarily conserved Transforming Growth Factor-beta; (TGF-beta;) signaling pathway plays a pivotal role in diverse cellular processes during growth and development. Impaired regulation of TGF-beta; signaling has been implicated in many human diseases and developmental defects. Although core components of the TGF-beta; pathway show significant structural and functional conservation across species, this has not been established for components that are involved in modulation of pathway activity. One of the goals of this study was to determine the role of Sloan-Kettering Institute/Ski-like Novel proteins (Ski/Sno) in Drosophila. Ski and Sno are negative regulators of TGF-beta; signaling in vertebrates, and have been implicated in oncogenesis. I identified Sno4 based on protein homology and carried out both loss-of-function and gain-of-function studies to understand its role in development. My studies suggest that Sno4 is a member of an emerging subfamily of Ski/Sno proteins that do not appear to participate in TGF-beta signaling. A second goal was to use a combined in silico screen and in vivo validation tests to identify target genes in the Bone Morphogenetic Protein (BMP) signaling pathway in flies. In particular, we focused on a BMP 2/4 ortholog, Decapentaplegic (Dpp) that belongs to the TGF-beta superfamily. Dpp signaling is implicated in multiple biological processes through out development in flies, however few direct transcriptional targets of the pathway are known. Dpp regulates transcription through the Schnurri/Mad/Medea (SMM) complex that is believed to mediate repression of Dpp target genes. An SMM consensus site was used to conduct a genome-wide screen that identified 460 potential Dpp targets. A subset of the sites were evaluated for their ability to mediate repression using reporter gene analysis. Reporters for two potential targets, ladybird early and frazzled, were investigated further and found to be Dpp responsive, and the SMM site was required to mediate repression. Therefore this was a useful strategy for identification of potential Dpp target genes. The work presented here not only provides novel insights into understanding the role of TGF-beta; in Drosophila, but also provides a powerful tool for identification of target genes in other pathway and organisms.