This book, published in association with the journal MOLECULAR AND CELLULAR BIOCHEMISTRY, is dedicated to Ed Krebs and Eddy Fischer in celebration of their 1992 Nobel Prize in Physiology and Medicine. Reversible protein phosphorylation is a research field pioneered and developed by Krebs and Fischer. This book contains short reviews and original research papers contributed by Krebs and Fischer's coworkers, both former and current. The contents reflect the two-way interaction between protein phosphorylation and other biomedical research fields. The chapters are grouped into four sections. The first two deal with structure/function aspects of protein kinases and protein mechanisms. Unlike many other research fields, which undergo periods of intense activity and productivity followed by relative calm, the protein phosphorylation field enjoyed continued growth both in scope and intensity, and the pace of this growth has increased markedly in recent years. This volume will provide a glimpse of the dynamism and diversity of the research activity representative of the current state of the field.

A Comprehensive Guide to Crucial Attributes of Therapeutic Proteins in Biological Pharmaceuticals With this book, Dr. Raju offers a valuable resource for professionals involved in research and development of biopharmaceutical and biosimilar drugs. This is a highly relevant work, as medical practitioners have increasingly turned to biopharmaceutical medicines in their search for safe and reliable treatments for complex diseases, while pharmaceutical researchers seek to expand the availability of biopharmaceuticals and create more affordable biosimilar alternatives. Readers receive a thorough overview of the major co-translational modifications (CTMs) and post-translational modifications (PTMs) of therapeutic proteins relevant to the development of biotherapeutics. The majority of chapters detail individual CTMs and PTMs that may affect the physicochemical, biochemical, biological, pharmacokinetic, immunological, toxicological etc. properties of proteins. In addition, readers are guided on the methodology necessary to analyze and characterize these modifications. Thus, readers gain not only an understanding of CTMs/PTMs, but also the ability to design and assess their own structure-function studies for experimental molecules. Specific features and topics include: Discussion of the research behind and expansion of biopharmaceuticals Twenty chapters detailing relevant CTMs and PTMs of proteins, such as glycosylation, oxidation, phosphorylation, methylation, proteolysis, etc. Each chapter offers an introduction and guide to the mechanisms and biological significance of an individual CTM or PTM, including practical guidance for experiment design and analysis An appendix of biologic pharmaceuticals currently on the market, along with an assessment of their PTMs and overall safety and efficacy This volume will prove a key reference on the shelves of industry and academic researchers involved in the study and development of biochemistry, molecular biology, biopharmaceuticals and proteins in medicine, particularly as biopharmaceuticals and biosimilars become ever more prominent tools in the field of healthcare.

Mitochondria are dynamic organelles that must rapidly adapt to changing cellular metabolic and biosynthetic demands. Until recently, mitochondria have represented an underappreciated site of regulation by reversible phosphorylation. Furthermore, the pathogenic alterations that underlie metabolic disorders have increasingly represented one of the principal challenges in cell biology. Our work has focused on using quantitative proteomics and phosphoproteomics to identify dynamic phosphorylation sites and characterize the function of phosphorylation on mitochondrial enzymes. We began by charting the remodeling of the mouse liver mitochondrial proteome and phosphoproteome during both acute and chronic physiological transformations in more than 50 mice. Our analyses reveal that reversible phosphorylation is widespread in mitochondria, and is a key mechanism for regulating ketogenesis during the onset of obesity and type 2 diabetes. Specifically, we demonstrated that phosphorylation of a conserved serine on Hmgcs2 (S456) significantly enhances its catalytic activity in response to increased ketogenic demand. Additionally, we used activity based protein profiling to identify kinases that are enriched in mitochondria, as well as kinases that are differentially enriched in the mitochondria of obese mice. We further report on the change in oxygen consumption rates in isolated mitochondria in response to treatment with calcium, and show that calcium uptake is also dependent on electron transport. We also show that phosphorylation sites in isolated mitochondria can be rapidly modulated by acute (10min) treatment with calcium as a stimulus. Finally, we performed multiplexed quantitative mass spectrometry to identify the targets of the mitochondrial phosphatase PTC7. Using yeast deletion strains, we identify over 50 putative phosphorylation sites that are unique to a deletion of PTC7. Furthermore, we demonstrate that phosphorylation of a conserved serine on Hem15, the final step in heme biosynthesis, decreases enzyme activity. Collectively, our work describes the plasticity of this organelle at high resolution and provides a framework for investigating the roles of proteome restructuring and reversible phosphorylation in mitochondrial adaptation.

The aim of this text is to integrate the processes of protein phosphorylation and dephosphorylation into the complex pathways by which cellular proliferation is driven, bringing together the many different systems of control implicated in the regulation of cell growth. Presents a survey of protein phosphorylation roles in the control of cellular proliferation and differentiation. A large number of protein kinases and phosphatases have been characterised in higher cells, and have been shown to be involved in signal transduction pathways by which growth factors, mitogens, and extracellular agents exert proliferative effects on cells. Important subjects covered include control of gene expression at the transcriptional and translational levels, and roles of the cdk kinases and cyclins in cell cycles regulation. Describes all major families of protein kinases of significance to growth regulation.

The NMDA receptor plays a critical role in the development of the central nervous system and in adult neuroplasticity, learning, and memory. Therefore, it is not surprising that this receptor has been widely studied. However, despite the importance of rhythms for the sustenance of life, this aspect of NMDAR function remains poorly studied. Written