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The actin cytoskeleton is critical to the proper function of cells and its misregulation can lead to human disease states. As a consequence, actin dynamics is tightly controlled. To gain further insight into the mechanisms controlling actin dynamics, my studies have focused on two families of proteins implicated in actin regulation.The Nck proteins act as molecular adaptors in signal propagation by linking upstream mediators, which they recognize through the Nck SH2 domain, to downstream effectors, which bind the Nck SH3 domains. I have found that Nck is required in podocyte cells for proper foot process formation, a process involving actin cytoskeletal reorganization, and therefore for proper kidney function. Furthermore, I show that Nck links the podocyte adhesion protein nephrin to actin polymerization. In cell-based assays, nephrin-induced actin polymerization is dependent on an interaction with functional Nck, which occurs through binding of three phosphorylated tyrosine sites within the cytoplasmic tail of nephrin to the Nck SH2 domain. Finally, I demonstrate that the enteropathogenic E.coli protein Tir reorganizes the cytoskeleton by molecular-mimicry of nephrin-like signaling.The srGAP proteins are GTPase activating proteins that attenuate the activity Rho GTPases, proteins directly involved in actin cytoskeletal control. The regulatory mechanisms that control srGAP activity are unclear. I have found that the srGAP family members srGAP1, srGAP2, and srGAP3 interact, through their carboxy-terminal region with 14-3-3 proteins, and that this interaction is dependent on protein kinase C-induced phosphorylation of srGAP. 14-3-3 binding does not affect the activity of srGAP2, as determined using cell-based GAP assays. Further studies are required to clarify the biological significance of this interaction to srGAP regulation.The data presented in this thesis furthers our understanding of signaling networks that control the actin cytoskeleton, and brings us closer to the goal of fully understanding actin dynamics and cellular signaling.
T cells play a vital role mediating adaptive immunity, a specific acquired resistance to an infectious agent produced by the introduction of an antigen. There are a variety of T cell types with different functions. They are called T cells, because they are derived from the thymus gland. This volume discusses how T cells are regulated through the operation of signaling mechanisms. Topics covered include positive and negative selection, early events in T cell receptor engagement, and various T cell subsets.
Handbook of Cell Signaling, Three-Volume Set, 2e, is a comprehensive work covering all aspects of intracellular signal processing, including extra/intracellular membrane receptors, signal transduction, gene expression/translation, and cellular/organotypic signal responses. The second edition is an up-to-date, expanded reference with each section edited by a recognized expert in the field. Tabular and well illustrated, the Handbook will serve as an in-depth reference for this complex and evolving field. Handbook of Cell Signaling, 2/e will appeal to a broad, cross-disciplinary audience interested in the structure, biochemistry, molecular biology and pathology of cellular effectors. Contains over 350 chapters of comprehensive coverage on cell signaling Includes discussion on topics from ligand/receptor interactions to organ/organism responses Provides user-friendly, well-illustrated, reputable content by experts in the field
A Practical Guide to the Study of Calcium in Living Cells describes popular techniques along with helpful do's and don't's and computer programs. The volume enables investigators to evaluate confocal images, use the latest dyes, and design Calcium buffers appropriate to their research needs. This book is designed for laboratory use by graduate students, technicians, and researchers in many disciplines, ranging from molecular to cellular levels of investigation. Describes techniques for detection of [Ca2+]I: Ca2+ - sensitive microelectrodes Fluorescent dyes Luminescent proteins Includes techniques for perturbing intracellular Ca2+ Covers detailed methodology plus problems and pitfalls of each technique Contains a practical guide to preparing Ca2+ buffers with an easy-to-use computer program Color plates illustrate techniques such as Confocal ratio-imaging Use of aequorin
Since the discovery of actin by Straub in the 1950’s and the pioneering work of Oosawa on actin self-assembly in helical laments in the 1960’s, many books and conference proceedings have been published. As one of the most essential p- teins in life, essential for movement in organisms rangingfrom bacteria to higher eukaryotes, it is no surprise that actin has fascinated generations of scientists from many different elds. Actin can be considered as a “living treasure” of biology; the kinetics and thermodynamics of self-assembly, the dissipative nature of actin po- merization, the molecular interactions of monomeric and polymerized actin with regulators, the mechanical properties of actin gels, and more recently the force p- ducing motile and morphogenetic processes organized by the actin nanomachine in response to signaling, are all milestones in actin research. Discoveries that directly derive from and provide deeper insight into the fundamental properties of actin are constantly being made, making actin an ever appealing research molecule. At the same time, the explosion in new technologies and techniques in biological sciences has served to attract researchers from an expanding number of disciplines, to study actin. This book presents the latest developments of these new multiscale approaches of force and movement powered by self-assembly processes, with the hope to opening our perspectives on the many areas of actin-based motility research.
This monograph explores the relationships between cell signaling and the cytoplasmic cytoskeleton in fundamental cell processes, thus bridging the gap between two very active aspects of molecular cell biology. It covers the two main - and reciprocal - questions of these relationships: How are structure and function of the cytoskeleton affected by external signals which impinge on the cell? How does the cytoskeleton influence the cellular signaling processes which determine cell behavior?
This book covers the past, present and future of the intra-cellular trafficking field, which has made a quantum leap in the last few decades. It details how the field has developed and evolved as well as examines future directions.
15 chapters on protein phosphorylation and human health written by expert scientists. Covers most important research hot points, such as Akt, AMPK and mTOR. Bridges the basic protein phosphorylation pathways with human health and diseases. Detailed and comprehensive text with excellent figure illustration.