Open Access Medical Books



Edited by Cai Huang .

Open Access .
478 pages .
ISBN 978-953-51-0737-8 .

Protein phosphorylation is a reversible posttranslational modification catalyzed by protein kinases and reversely by protein phosphatases. There are about 500 protein kinases and 25-30 phosphatases in human genome. Each kinase and phosphatase targets multiple substrates. Thus, protein phosphorylation is a most versatile signaling regulatory mechanism and constitutes a most complicated signaling network in living organisms. In fact, protein phosphorylation governs all aspects of physiological and pathological processes in human health. During last decades, more than 180,000 scientific papers on protein phosphorylation have been published. To handle and digest so much knowledge and information is a big challenge to our students, college teachers and investigators. Therefore, we invited expert scientists to write 15 chapters on specific fields of protein phosphorylation where their expertise lies. We also asked our authors to relate their protein phosphorylation pathways to human health. We hope that this book could be a good hand for our students, teachers and investigators who want to extend their knowledge on the role of protein phosphorylation in human health. Please also keep in mind that no any single book can cover all aspects of protein phosphorylation pathways.
The chapters have been organized into 5 different sections, based on the similarity of protein phosphorylation pathways. The first section has 4 chapters summarizing on the role of Akt, mTOR and AMPK in cancer and metabolic disorders. The section focuses on the structure, function and regulation of mTOR1 and mTOR2 and their role in cancer, neurodegeneration, and diabetes, the role of Sestrins, a family of stressresponsive genes in regulating AMPK-mTOR pathway and their role in cardiovascular diseases, muscle- and neuro- degeneration, diabetes and cancer, the signaling pathways that regulate autophagy, including Akt, AMPK and mTOR, and the role of Akt/AMPK and PI3K/Erk pathways in fatty acids-stimulated glucose uptake. The second section has 4 chapters reviewing the role of protein phosphorylation in transcription, pre-mRNA splicing and DNA damage. The section emphasizes the regulation of RNA polymerase II sequentially by protein kinases and phosphatases in gene expression and therapeutically potentials, the genetic interactions, biochemical properties, and substrate specificity of Prp4 kinase and its role in pre-mRNA splicing, the regulation of Trk/Erk/CREB pathway by BDNF and the role in neuronal growth, synaptic plasticity and cell survival, and the signaling pathways in regulating DNA damage. The third section has 4 chapters covering the role of protein tyrosine kinases in receptor signaling and human diseases. This section accentuates the tyrosine phosphorylation of NMDA receptor by Src family kinases and its role in cerebral ischaemia, the role of flotillins in regulating receptor tyrosine kinase and in cancer, Alzheimer’s Disease and diabetes, the role of TrkA/PKCθ/Erk pathway in alpha-toxinmediated inflammation, and distinct regulation of HER2 tyrosine/threonine phosphorylation by trastuzumab (anti-HER2 monoclonal antibody) and lapatinib (small molecule HER2/1 tyrosine kinase inhibitor). The fourth section has 2 chapters: one summarizes the regulation of cdc25 phosphatase by phosphorylation during cellcycle and DNA damage, and another illustrates the role of protein phosphorylation in cell cycle regulation using Swe1, Kin4, Cyk3, Hof1 and Chs2 as examples. The fifth section has only 1 chapter describing the role of histidine kinases in the bacterium twocomponent system.
The study on protein phosphorylation is one of most exciting fields in biomedical research. This book provides detailed and comprehensive review on 5 different areas of protein phosphorylation signaling pathways and their roles in human health. This book is our attempt to bridge the basic phosphorylation pathways with human health and diseases. We hope that this book will be of help to students, teachers and researchers who need to deepen their knowledge in these specific areas and promote progress in multi-disciplines of biomedical science.

Cai Huang, Ph.D.
Markey Cancer Center 
and Department of Molecular & Biomedical Pharmacology,
University of Kentucky,


Section 1 Akt, mTOR and AMPK in Cancer and Metabolic Disorders .

 1 Protein Phosphorylation as a Key Mechanism of mTORC1/2 Signaling Pathways 3 Elena Tchevkina and Andrey Komelkov

 2 Sestrins Link Tumor Suppressors with the AMPK-TOR Signaling Network 51 Andrei V. Budanov

 3 Regulation of Autophagy by Protein Phosphorylation 97 Björn Stork, Sebastian Alers, Antje S. Löffler and Sebastian Wesselborg

 4 Fatty Acids Stimulate Glucose Uptake by the PI3K/AMPK/Akt and PI3K/ERK1/2 Pathways 129 Jing Pu and Pingsheng Liu

Section 2 Protein Phosphorylation in Transcription, pre-mRNA Splicing and DNA Damage .

 5 RNA Polymerase II Phosphorylation and Gene Expression Regulation 151 Olga Calvo and Alicia García

 6 The Prp4 Kinase: Its Substrates, Function and Regulation in Pre-mRNA Splicing 195 Martin Lützelberger and Norbert F. Käufer

 7 More Than Just an OFF-Switch: The Essential Role of Protein Dephosphorylation in the Modulation of BDNF Signaling Events 217 Katrin Deinhardt and Freddy Jeanneteau

 8 Signalling DNA Damage 233 Andres Joaquin Lopez-Contreras and Oscar Fernandez-Capetillo

Section 3 Tyrosine Protein Kinases in Receptor Signaling and Diseases .

 9 Tyrosine Phosphorylation of the NMDA Receptor Following Cerebral Ischaemia 265 Dmytro Pavlov and John G. Mielke

 10 Function of Flotillins in Receptor Tyrosine Kinase Signaling and Endocytosis: Role of Tyrosine Phosphorylation and Oligomerization 307 Nina Kurrle, Bincy John, Melanie Meister and Ritva Tikkanen

 11 Role of Tyrosine Kinase A Receptor (TrkA) on Pathogenicity of Clostridium perfringens Alpha-Toxin 343 Masataka Oda, Masahiro Nagahama, Keiko Kobayashi and Jun Sakurai

 12 Modulation of HER2 Tyrosine/Threonine Phosphorylation and Cell Signalling 357 Yamuna D. Gandaharen, Rachel S. Welt, David Kostyal and Sydney Welt

Section 4 Protein Kinases and Phosphatases in Cell Cycle Regulation .

 13 Protein Phosphorylation is an Important Tool to Change the Fate of Key Players in the Control of Cell Cycle Progression in Saccharomyces cerevisiae 377 Roberta Fraschini, Erica Raspelli and Corinne Cassani

 14 Phosphorylation Mediated Regulation of Cdc25 Activity, Localization and Stability 395 C. Frazer and P.G. Young

Section 5 Histidine Kinases in Two-Component Systems .

 15 Bacterial Two-Component Systems: Structures and Signaling Mechanisms 439 Shuishu Wang .

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Published by: Unknown - Sunday, June 23, 2013


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