Inositol Lipids In Cellular Signaling

The discovery that inositol lipids are integral in cellular signaling mechanisms has been one of the most exciting breakthroughs in recent years. As secondary messengers in a wide variety of tissues and involved processes as diverse as rapid contraction of skeletal muscle, insulin secretion, and the slow activation of cell proliferation in cancer cells, their impact on biochemistry is akin to that of cyclic AMP two decades ago. Drawing together the many strands of research on inositol lipid-mediated signalling and containing contributions by leading authorities in their fields, Inositol Lipids in Cell Signalling is essential for any involved biochemist, cell biologist, or pharmacologist.

This book provides the most updated information of how membrane lipids mediate protein signaling from studies carried out in animal and plant cells. Also, there are some chapters that go beyond and expand these studies of protein-lipid interactions at the structural level. The book begins with a literature review from investigations associated to sphingolipids, followed by studies that describe the role of phosphoinositides in signaling and closing with the function of other key lipids in signaling at the plasma membrane and intracellular organelles.

Lipids are best known as energy storing molecules and core-components of cellular membranes, but can also act as mediators of cellular signaling. This is most prominently illustrated by the paramount importance of the phospholipase C (PLC) and phosphoinositide 3-kinase (PI3K) signaling pathways in many cells, including T cells and cancer cells. Both of these enzymes use the lipid phosphatidylinositol(4,5)bisphosphate (PIP2) as their substrate. PLCs produce the lipid product diacylglycerol (DAG) and soluble inositol(1,4,5)trisphosphate (IP3). DAG acts as a membrane tether for protein kinase C and RasGRP proteins. IP3 is released into the cytosol and controls calcium release from internal stores. The PI3K lipid product phosphatidylinositol(3,4,5)trisphosphate (PIP3) controls signaling by binding and recruiting effector proteins such as Akt and Itk to cellular membranes. Recent research has unveiled important signaling roles for many additional phosphoinositides and other lipids. The articles in this volume highlight how multiple different lipids govern T cell development and function through diverse mechanisms and effectors. In T cells, lipids can orchestrate signaling by organizing membrane topology in rafts or microdomains, direct protein function through covalent lipid-modification or non-covalent lipid binding, act as intracellular or extracellular messenger molecules, or govern T cell function at the level of metabolic regulation. The cellular activity of certain lipid messengers is moreover controlled by soluble counterparts, exemplified by symmetric PIP3/inositol(1,3,4,5)tetrakisphosphate (IP4) signaling in developing T cells. Not surprisingly, lipid producing and metabolizing enzymes have gained attention as potential therapeutic targets for immune disorders, leukemias and lymphomas.

This volume in the well-established Methods in Enzymology series features methods for the study of lipids using mass spectrometry techniques. Articles in this volume cover topics such as Phospholipase A1 assays using a radio-labeled substrate and mass spectrometry; Real-time Cell Assays of Phospholipases A2 Using Fluorogenic Phospholipids; Analysis and Pharmacological Targeting of Phospholipase C â interactions with G proteins; Biochemical Analysis of Phospholipase D.; Measurement of Autotaxin/Lysophospholipase D Activity; Platelet-Activating Factor; Quantitative measurement of PtdIns(3,4,5)P3; Measuring Phosphorylated Akt And Other Phosphoinositide 3-Kinase-Regulated Phosphoproteins In Primary Lymphocytes; Regulation of Phosphatidylinositol 4-Phosphate 5-Kinase activity by partner proteins; Biochemical Analysis of Inositol Phosphate Kinases; Analysis of the phosphoinositides and their aqueous metabolites; Combination of C17-sphingoid base homologues and mass spectrometry analysis as a new approach to study sphingolipid metabolism; Measurement of mammalian sphingosine-1-phosphate phosphohydrolase activity in vitro and in vivo; A rapid and sensitive method to measure secretion of sphingosine-1-phosphate; Ceramide Kinase and Ceramide-1-Phosphate; Measurement of Mammalian Diacylglycerol Kinase Activity in vitro and in Cells; Lipid Phosphate Phosphatases from Saccharomyces cerevisiae.

Phospholipids are no longer considered exclusively as the building blocks of biomembranes, but are now regarded to be exceptionally important to cellular signalling.Another conclusion resulting from studies over the past several years is that no single general scheme for the role of phospholipids during cell activation can be drawn as representative of all cells. This book presents a comprehensive view of the recent advances made in certain major research areas within the field of phospholipid metabolism in cellular signalling. Topics discussed within this volume include lipid composition of cellular membranes and their organization in biological systems, the dynamic aspects of phospholipid metabolism and its regulation by extracellular stimuli, and the role of newly discovered glycosyl-phosphatidylinositols in insulin action . The book also discusses two biologically active phospholipids: the sphingolipids, and ether-linked glycerophospholipids (the platelet activating factor). Phospholipid Metabolism in Cellular Signaling is an important research reference that should be considered required reading by all scientists and graduate students working on cell activation (e.g., growth factors, hormones, and oncogenes).

Many of the phospholipases and even the receptor for inositol 1,4,5-trisphosphate have recently been cloned and sequenced and play an important role in neurotransmission. Methods developed in recent years for the study of the enzymes and intermediates involved in the regulation of neuronal signal transduction involving phospholipid turnover are presented in this volume. Techniques for examining the role of phosphoinositides in signal transduction Techniques related to protein kinase C Analysis of inositol phosphates Techniques to analyze phospholipid turnover in the brain