Proteins and Cell Regulation – serie

For the first time experts in the area of signalling research with a focus on the ARF family have contributed to the production of a title devoted to ARF biology. A comprehensive phylogenetic analysis of the ARF family, tables of the ARF GEFs and ARF GAPs, and more than a dozen chapters describing them in detail are provided. The impact of the ARF proteins on widely diverse aspects of cell biology and cell signalling can be clearly seen from the activities described; including membrane traffic, lipid metabolism, receptor desensitization, mouse development, microtubule dynamics, and bacterial pathogenesis. Anyone interested in understanding the complexities of cell signalling and the integration of signalling networks will benefit from this volume.

This volume represents the first collection of articles contributed by research leaders working on the Myb family of transcriptional regulatory proteins. In more than twenty chapters the authors discuss the range of biological processes and diverse cell types in which Myb proteins operate. Although concentrating on the three vertebrate Myb family members, homologues from lower species are also discussed because of the light they are able to shed on the evolution and function of these proteins. Individual chapters describe the involvement of Myb proteins, in particular c-Myb, in normal and diseased development and function of many tissues including haemopoietic cells, blood vessels, the gastrointestinal tract and the brain. Several chapters explore the mechanistic details of the action of Myb proteins, especially structural features, their interaction with DNA and other regulatory proteins, and the variety of genes that are regulatory targets for this group of transcription factors. This work will be of interest to those working directly in the field and also to the wider research community investigating the transcriptional regulation of development, differentiation and growth. The therapeutic potential of manipulating Myb function is also discussed making the book appealing to clinician scientists in several fields including haematology, oncology and cardiology.

Humans contain more than 20 Rho type GTPases. This volume not only presents a detailed phylogenetic analysis of Rho proteins, but also discusses the possible origins of the human members. Such an analysis of human Rho GTPases has not previously been attempted.The book includes an overview of how Rho GTPases become activated which is complemented by an extensive Chapter by Darerca Owen and Helen Mott who unravel the beautiful molecular details given to us by the many structural studies of Rho GTPases.The key areas currently being investigated in relation to these ubiquitous proteins are described for both in vitro and in vivo systems. These are presented in a format that ensures the reader can approach the topic with minimal background knowledge, while ultimately bringing the subject to the level of an expert. Timely and highly authoritative, this volume illuminates newer findings, particularly as they relate to Rho proteins in vertebrate biology.

Since 1982, Ras proteins have been the subject of intense research investigation by the biomedical research community. The wide interest in Ras has been stimulated for three key reasons.First, their frequent mutational activation in human cancers establishes Ras proteins as important mediators of oncogenesis and targets for anti-cancer drug discovery. Second, Ras proteins act as signalling nodes activated by diverse extracellular stimuli, and activated Ras in turn regulates a diversity of cytoplasmic signalling networks. Third, Ras proteins are founding members of a large superfamily of Ras-related small GTPases. Over 150 Ras-related small GTPases are found in the human genome, with orthologs found in all vertebrate species and invertebrates.This book features chapters by leading investigators in the field that highlight the current state-of-the art in Ras biochemistry, structure and biology. This book is an excellent reference for students in the biomedical sciences and for investigators in the field.

For the first time world-leading experts in the area of cellular signaling have joined to the production of a book on Smad signal transduction. Smads are the principal intracellular effectors of TGF-b family members that control numerous cellular responses with critical roles in development and in tissue homeostasis. In a series of 22 cutting-edge chapters forward looking reviews of Smads are provided that cover their discovery, evolution, role in development, mechanism of action and regulation, and how deregulation in Smad signalling contributes to human diseases. 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. This book will be of particular interest to basic and applied biomedical researchers (students, post-docs or group leaders) with desire to understand the principles of cell-cell communication and mechanisms by which signaling pathways and gene programs control cell proliferation and differentiation, and how this knowledge may come to be applied in the clinic.

Few would have predicted 20 years ago that myosins constitute a superfamily with at least two-dozen classes and that these molecular motors are involved in a multitude of intracellular activities including cell division, cell movement, intracellular transport and signal transduction. Application of state-of-the-art cellular and molecular biological, structural biological, genetic, biochemical and biophysical techniques has provided and continues to provide critical information regarding the structure–function relationship; and the cellular roles of various myosins in organisms as diverse as protozoa, yeast, plants and higher animals. The association of myosins with diseases including neurological disorders, immu- deficiencies, cardiomyopathies, hearing and vision loss testify to the importance of understanding the biochemical properties and cellular roles of myosins. The 16 chapters in this volume summarize the tremendous progress made in studying members of the myosin superfamily in recent years and offer critical insight into what future research will yield. I would like to express my sincere gratitude to the authors of this volume. It was a pleasure to work with each of you and I thank you for the considerable efforts in making this international endeavor possible. I also thank John Trinick from the University of Leeds, UK, for the elegant montage of images of single molecules of myosins on the cover, which beautifully shows the structures of some of these amazing molecules. The able assistance of Marlies Vlot from Springer and Indumadhi Srinivasan from Integra Software Services for production of the book is greatly appreciated.

Research into the paraoxonase (PON) multigene family has really only blossomed in the last 10 years. Before this time only PON1 was known and research was restricted to toxicologists investigating the metabolism of organophosphate insecticides and nerve gases and a few “mad” scientists searching for “natural” substrates.Since this time two new members PON2 and PON3 have been discovered, all 3 PONs have been shown to act as antioxidants and the PON family has taken centre stage as major players in the development of a wide variety of diseases such as cardiovascular disease, diabetes mellitus, rheumatism, Alzheimer and many more while remaining important in determining organophosphate toxicity.In September 2006 the 2nd International Conference on Paraoxonases took place in Hajdúszoboszló, Hungary, bringing together the world's foremost experts in the field. The current book is a distillation of the plenary lectures which took place at the meeting, resulting in a comprehensive up to date, state of the art review of current paraoxonase research.

In 1890 a case of myxedema was treated in Lisbon by the implantation of a sheep thyroid gland with the immediate improvement in the patient’s condition. A few years later, medications for the then ill-explained condition of the menopause included tablets made from cow ovaries. In the first quarter of the 20th century the identification of vitamin D, and its sunlight driven production in skin, paved the way to the elimination of rickets as a major medical problem. Twenty years or so later, Sir Vincent Wigglesworth established the endocrine basis of developmental moulting in insects, arguably the most commonly performed animal behaviour on Planet Earth. A paradigm that would unify these disparate observations arose between 1985 and 1987 beginning with the identification of the glucocorticoid receptor and the nuclear receptor super-family. What follows is a timely and positive manifestation of the capacity, productivity and value of international human scientific endeavour. Based on intrigue, lively competition and cooperation a global effort has rapidly fostered a school of biology with widespread ramifications for the understanding of metazoan animals, the human condition and the state of the planet. This book is the first this century to try and capture the spirit of this endeavour, to depict where the field is now and to identify some of the challenges and opportunities for the future.

For the first time experts in the area of signalling research with a focus on the ARF family have contributed to the production of a title devoted to ARF biology. A comprehensive phylogenetic analysis of the ARF family, tables of the ARF GEFs and ARF GAPs, and more than a dozen chapters describing them in detail are provided. The impact of the ARF proteins on widely diverse aspects of cell biology and cell signalling can be clearly seen from the activities described; including membrane traffic, lipid metabolism, receptor desensitization, mouse development, microtubule dynamics, and bacterial pathogenesis. Anyone interested in understanding the complexities of cell signalling and the integration of signalling networks will benefit from this volume.

This volume represents the first collection of articles contributed by research leaders working on the Myb family of transcriptional regulatory proteins. In more than twenty chapters the authors discuss the range of biological processes and diverse cell types in which Myb proteins operate. Although concentrating on the three vertebrate Myb family members, homologues from lower species are also discussed because of the light they are able to shed on the evolution and function of these proteins. Individual chapters describe the involvement of Myb proteins, in particular c-Myb, in normal and diseased development and function of many tissues including haemopoietic cells, blood vessels, the gastrointestinal tract and the brain. Several chapters explore the mechanistic details of the action of Myb proteins, especially structural features, their interaction with DNA and other regulatory proteins, and the variety of genes that are regulatory targets for this group of transcription factors. This work will be of interest to those working directly in the field and also to the wider research community investigating the transcriptional regulation of development, differentiation and growth. The therapeutic potential of manipulating Myb function is also discussed making the book appealing to clinician scientists in several fields including haematology, oncology and cardiology.

Humans contain more than 20 Rho type GTPases. This volume not only presents a detailed phylogenetic analysis of Rho proteins, but also discusses the possible origins of the human members. Such an analysis of human Rho GTPases has not previously been attempted. The book includes an overview of how Rho GTPases become activated which is complemented by an extensive Chapter by Darerca Owen and Helen Mott who unravel the beautiful molecular details given to us by the many structural studies of Rho GTPases. The key areas currently being investigated in relation to these ubiquitous proteins are described for both in vitro and in vivo systems. These are presented in a format that ensures the reader can approach the topic with minimal background knowledge, while ultimately bringing the subject to the level of an expert. Timely and highly authoritative, this volume illuminates newer findings, particularly as they relate to Rho proteins in vertebrate biology.

Since 1982, Ras proteins have been the subject of intense research investigation by the biomedical research community. The wide interest in Ras has been stimulated for three key reasons.First, their frequent mutational activation in human cancers establishes Ras proteins as important mediators of oncogenesis and targets for anti-cancer drug discovery. Second, Ras proteins act as signalling nodes activated by diverse extracellular stimuli, and activated Ras in turn regulates a diversity of cytoplasmic signalling networks. Third, Ras proteins are founding members of a large superfamily of Ras-related small GTPases. Over 150 Ras-related small GTPases are found in the human genome, with orthologs found in all vertebrate species and invertebrates.This book features chapters by leading investigators in the field that highlight the current state-of-the art in Ras biochemistry, structure and biology. This book is an excellent reference for students in the biomedical sciences and for investigators in the field.

For the first time world-leading experts in the area of cellular signaling have joined to the production of a book on Smad signal transduction. Smads are the principal intracellular effectors of TGF-b family members that control numerous cellular responses with critical roles in development and in tissue homeostasis. In a series of 22 cutting-edge chapters forward looking reviews of Smads are provided that cover their discovery, evolution, role in development, mechanism of action and regulation, and how deregulation in Smad signalling contributes to human diseases. 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. This book will be of particular interest to basic and applied biomedical researchers (students, post-docs or group leaders) with desire to understand the principles of cell-cell communication and mechanisms by which signaling pathways and gene programs control cell proliferation and differentiation, and how this knowledge may come to be applied in the clinic.

Research into the paraoxonase (PON) multigene family has really only blossomed in the last 10 years. Before this time only PON1 was known and research was restricted to toxicologists investigating the metabolism of organophosphate insecticides and nerve gases and a few “mad” scientists searching for “natural” substrates.Since this time two new members PON2 and PON3 have been discovered, all 3 PONs have been shown to act as antioxidants and the PON family has taken centre stage as major players in the development of a wide variety of diseases such as cardiovascular disease, diabetes mellitus, rheumatism, Alzheimer and many more while remaining important in determining organophosphate toxicity.In September 2006 the 2nd International Conference on Paraoxonases took place in Hajdúszoboszló, Hungary, bringing together the world's foremost experts in the field. The current book is a distillation of the plenary lectures which took place at the meeting, resulting in a comprehensive up to date, state of the art review of current paraoxonase research.

In 1890 a case of myxedema was treated in Lisbon by the implantation of a sheep thyroid gland with the immediate improvement in the patient’s condition. A few years later, medications for the then ill-explained condition of the menopause included tablets made from cow ovaries. In the first quarter of the 20th century the identification of vitamin D, and its sunlight driven production in skin, paved the way to the elimination of rickets as a major medical problem. Twenty years or so later, Sir Vincent Wigglesworth established the endocrine basis of developmental moulting in insects, arguably the most commonly performed animal behaviour on Planet Earth. A paradigm that would unify these disparate observations arose between 1985 and 1987 beginning with the identification of the glucocorticoid receptor and the nuclear receptor super-family. What follows is a timely and positive manifestation of the capacity, productivity and value of international human scientific endeavour. Based on intrigue, lively competition and cooperation a global effort has rapidly fostered a school of biology with widespread ramifications for the understanding of metazoan animals, the human condition and the state of the planet. This book is the first this century to try and capture the spirit of this endeavour, to depict where the field is now and to identify some of the challenges and opportunities for the future.

Tetraspanin proteins have recently emerged as a new class of modulators of various processes involving cell surface receptors, including cell migration and invasion, host immune responses, cell-cell fusion, and viral infection. The book summarises recent advances in the fields of biology in which the role of tetraspanins have been established and also covers the molecular evolution of the tetraspanin superfamily and structural aspects of the organisation of tetraspanin microdomains.

Tetraspanin proteins have recently emerged as a new class of modulators of various processes involving cell surface receptors, including cell migration and invasion, host immune responses, cell-cell fusion, and viral infection. The book summarises recent advances in the fields of biology in which the role of tetraspanins have been established and also covers the molecular evolution of the tetraspanin superfamily and structural aspects of the organisation of tetraspanin microdomains.

The sirtuin family of proteins (SIRT1-7) received a lot of attention in recent years as they serve as metabolic sensors that control not only metabolism, but also aging and lifespan regulation. As such, sirtuins are strong targets for the treatment of age-related metabolic diseases, including obesity, diabetes, and cancer. Indeed, many research groups as well as pharmaceutical companies discovered food components and/or drugs that target the sirtuins and provide significant health benefits. This book focuses on various aspects of sirtuin biology, from basic biochemistry, via molecular function, to its role in (fighting) human disease.