• Phospholipase Cs participate in phosphatidylinositol 4,5-bisphosphate (PIP2) metabolism and lipid signaling pathways in a calcium-dependent manner. (wikipedia.org)
  • This focus reflects the unique aspects and incredible diversity of lipids and their associated enzymes in regulating signaling pathways, membrane environments, metabolic pathways, and gene transcription to affect physiology and pathophysiology. (grc.org)
  • The regulated production of lipid second messengers is critical for the coordinated functioning of a cell, and various systems such as feedback regulation and signal convergence from multiple pathways help to ensure that disruption of a single lipid metabolizing enzyme does not compromise the intricate communications network. (johnshopkins.edu)
  • Rather, metabolism is a driver of cell fate , and failure to engage essential metabolic pathways results in dysfunction and cell death. (unibas.ch)
  • Under physiological conditions, TRPML1 regulates membrane trafficking by transducing information about levels of PI(3,5)P2, a low-abundance endolysosome-specific phosphoinositide, into changes in juxtaorganellar Ca2+, thereby triggering membrane fusion events in the late endocytic pathways. (nih.gov)
  • We investigate signal transduction pathways that mediate the actions of hormones, growth factors, and neurotransmitters in mammalian cells, with special emphasis on the role of phosphoinositide-derived messengers. (nih.gov)
  • Our aims involve developing innovative approaches to prevent visual loss through manipulation of metabolic reprogramming, use of lipid-nanotechnology, stem-cell implantation, and activation of endogenous neuroprotective pathways. (dmei.org)
  • How cells generate and maintain the specific lipid composition of their organelles against complex and highly dynamic vesicular transport pathways is a fundamental question at the intersection of lipid and cell biology. (asbmb.org)
  • and phosphoinositide (PI) 3′-kinase and Ral-guanine nucleotide dissociation stimulator (Ral-GDS) which activate lipid pathways (2). (ecologicalsgardens.com)
  • Many of the genes commonly mutated encode Purpose and scope INTRODUCTION components or targets of the PI3K/AKT and Ras/ERK pathways, causing dysregulation of cellular signaling.1 This dysregulation drives cancer progression by influencing the behavior of tumor cells through cell proliferation, survival, migration, differentiation, metabolism, polarity, angiogenesis, and the tumor microenvironment. (technologynetworks.com)
  • These observations provide collective evidence that therapeutic responses are primarily linked to such pathways as regulation of lipid and amino acid metabolism, TCA cycle and glycolysis, advocating therefore the development of further effective targeted therapies against a broader spectrum of TKs to treat patients whose tumors display deregulated signalling driven by these proteins. (biomedcentral.com)
  • As aforementioned, accumulating evidence suggests that key oncogenic pathways program the adaptation of metabolism with explicit changes for the selective advantage of tumor cells, many of them regulated by tyrosine kinase activity [ 14 , 15 , 16 ]. (biomedcentral.com)
  • mRNA levels of AMPK, insulin receptor substrate (IRS), phosphoinositide-3-phosphate kinase (PI3K), Akt, and glucose transporter 2 (GLUT2) were measured using real-time polymerase chain reaction. (phcog.com)
  • In streptozotocin-induced diabetic rats, PHF improves glucose and lipid metabolism by attenuating hyperglycemia, hyperinsulinemia, dyslipidemia, insulin resistance, oxidative stress, inflammation, and deterioration of hepatic architecture possibly through AMPK mediated improvement in hepatic IRS-PI3K-Akt-GLUT2 signaling pathway. (phcog.com)
  • One of the most robust biochemical signals elicited by chemokines in T-lymphocytes is the activation of several members of the PI3K (phosphoinositide 3-kinase) family. (silverchair.com)
  • The role of phosphoinositide-3-kinase (PI3K)/protein-kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in tumorigenesis has been investigated thoroughly in the past years. (por-journal.com)
  • Association of peripheral proteins with lipid bilayers regulates membrane signaling and dynamics. (nih.gov)
  • citation needed] This catalytic process is tightly regulated by reversible phosphorylation of different phosphoinositides and their affinity for different regulatory proteins. (wikipedia.org)
  • This mechanism is based on the unique ability of PI4P to selectively occupy the binding pocket of several dedicated lipid transfer proteins that belong to the superfamily of oxysterol-binding protein (OSBP)-related proteins, or ORPs. (nih.gov)
  • PI4P binds with high affinity to these lipid transfer proteins, allowing loading of their specific lipid cargo only in the endoplasmic reticulum (ER), an organelle devoid of PI4P because of the presence of a PI4P dephosphorylating phosphatase, Sac1. (nih.gov)
  • Phosphoinositides regulate protein kinases and GTP-binding proteins as well as membrane transporters, including ion channels, thereby controlling many cellular processes such as proliferation, apoptosis, metabolism, cell migration, and differentiation. (nih.gov)
  • M. Laura Salto (UIUC, Urbana) showed that inositolphosphoceramide, a lipid used in anchoring several proteins to the plasma membrane of T. cruzi and absent in the host, is remodeled during the differentiation of different stages of the parasite. (medscape.com)
  • Tryptophan metabolism in mosquitoes and the separation and identification of mosquito chrorion proteins through two-dimensional electrophoresis and mass spectrometry will provide useful targets against these vectors of several infectious diseases, as reported by Jianyong Li and his collaborators (UIUC, Urbana). (medscape.com)
  • We created fusion proteins consisting of the green fluorescent protein and small protein modules known to confer specific inositol lipid interactions. (nih.gov)
  • Other lipid compounds bind to sugars or proteins to form glycolipids or lipoproteins, which perform unique biological functions. (creative-proteomics.com)
  • Together, our identification of a unique family of Legionella PI phosphatases highlights a common scheme of exploiting host PI lipids in many intracellular bacterial pathogen infections. (rcsb.org)
  • PPIns were first recognized in the mid-1970's and early 1980's as important lipid precursors that are found in the plasma membrane (PM) and directly contributed to the formation of intracellular signaling molecules when cells respond to external cues such as hormones, neurotransmitters, nutrients, or even light (2). (nih.gov)
  • Members of the chemokine superfamily play a key role in providing navigational cues for T-cells and chemokine receptors couple with a wide range of biochemical signals including phosphoinositide lipid metabolism, elevation of intracellular calcium levels, activation of a wide array of protein kinases as well as small GTPases. (silverchair.com)
  • Phosphoinositides constitute a small fraction of the cellular phospholipids but play critical roles in the regulation of many signaling protein complexes that assemble on the surface of cellular membranes and are intracellular lipid messengers controlling a variety of cellular functions. (nih.gov)
  • Structural Mechanisms of Activation of Phosphoinositide 3-Kinase Superfamily Enzymes on Membranes. (grc.org)
  • Among PPIns, PI 4-phosphate (PI4P), which bears a phosphate at the 4-position of the inositol ring of PI, has recently been shown to play a critical role in the non-vesicular transport of lipids between membranes of various organelles (5). (nih.gov)
  • As it turns out, PI4P gradients can be established between two neighboring membranes at sites of close apposition, which are commonly called membrane contact sites (MCS), and used to drive the counter-transport of other lipid species against their concentration gradients. (nih.gov)
  • A strong body of evidence suggests that a large network of signaling enzymes, called lipid kinases, can add phosphate tags onto components of cellular membranes and are essential hubs for regulating cell metabolism. (europa.eu)
  • The unique lipid composition of different membranes defines organelle identity and is critical for protein-membrane interactions. (asbmb.org)
  • Lipid compounds can be used as cellular constituents, the most important of which is as structural components of cell membranes. (creative-proteomics.com)
  • The protein phosphorylation-driven conformational change of p47(phox) enables its PX domain to bind to phosphoinositides, the interaction of which plays a crucial role in recruitment of p47(phox) from the cytoplasm to membranes and subsequent activation of the phagocyte oxidase. (embl.de)
  • Phosphatidylinositol (PtdIns or PI) has two fatty acyl side chains (usually stearic acid and arachidonic acid in the sn-1 and sn-2 positions, respectively) embedded in the membrane lipid bilayer and an inositol headgroup that is exposed at the surface of the membrane. (nih.gov)
  • Towards understanding non-canonical phosphatidylinositol kinases in the maintenance of prostate metabolism. (europa.eu)
  • The current work of my research group was initiated by studies in the mid-1990s when we observed that the phosphoinositide precursors for receptor-mediated production of Ins(1,4,5)P 3 are synthesized by a phosphatidylinositol 4-kinase (PI4K) activity that is sensitive to PI 3-kinase inhibitors, such as wortmannin. (nih.gov)
  • On the receiving side of the MCS, where lipids to be delivered, the PI 4-kinases (or PI4Ks) phosphorylate PI at the 4-position creating high levels of PI4P. (nih.gov)
  • and (5) determine the importance of the lipid-protein interactions in the activation of cellular responses by G protein-coupled receptors and receptor tyrosine kinases. (nih.gov)
  • Herein, I propose exploring PI5P4K lipid kinases in PCa. (europa.eu)
  • I believe PI5P4K lipid kinases are unexplored cornerstones of cell metabolism and aim to be the first to establish their role in prostate biology. (europa.eu)
  • 4-HNE and 9-nitrooleic acid were also found to activate Erk1/2, JNK and p38 MAP kinases, as well as phosphoinositide-3-kinase (PI3)/Akt. (nih.gov)
  • Src and Abl), lipid kinases (e.g. phosphoinositide 3-kinases, PI3Ks), as well as nuclear receptors (e.g. the estrogen receptor). (technologynetworks.com)
  • These changes consist of upregulated glycolysis (even in the presence of oxygen) also known as the "Warburg-effect," increased glutaminolysis and lactate synthesis, alterations in lipid metabolism, and tricarboxylic acid cycle/oxidative phosphorylation. (por-journal.com)
  • The cornea is highly sensitive to oxidative stress, a process that can lead to lipid peroxidation. (nih.gov)
  • Therefore, AdipoR1 and R2 serve as the predominant receptors for adiponectin in vivo and play important roles in the regulation of glucose and lipid metabolism, inflammation and oxidative stress in vivo . (nature.com)
  • While studying the functions and regulation of these enzymes, which are found in distinct cellular compartments, I explored new ways to examine localized production of inositol lipids and follow their dynamics in intact single cells. (nih.gov)
  • By expressing these modules specific for particular inositol lipids, we were able to track production and localization of several lipids in intact cells (see figure). (nih.gov)
  • In turn, metabolic information is translated to signaling circuits driven by phosphoinositide metabolism. (tamu.edu)
  • Our data demonstrated a novel role of Pik3r1 that was independent of the regulatory function of phosphoinositide 3-kinase in mediating the metabolic action of glucocorticoids. (nih.gov)
  • Fibroblast growth factor 21 (FGF21), a secretion protein, functions as a pivotal regulator of energy metabolism and is being considered as a therapeutic candidate in metabolic syndromes. (hindawi.com)
  • The use of lipidomics to study the relationship between changes in lipid metabolic network and disease states at the systemic level, to find potential biomarkers, and to evaluate the efficacy of new drugs has become a new development direction. (creative-proteomics.com)
  • In this review, we discuss recent observations related to TKs-associated metabolism and to metabolic feedback that is initialized as cellular response to particular TK-targeted therapies. (biomedcentral.com)
  • In recent years, in addition to investigating the role of cell metabolism in tumor cell development, particular attention has been devoted to metabolic changes occurring as a response to targeted treatments [ 5 , 6 , 7 ]. (biomedcentral.com)
  • In view of the role that TKs seem to play in the regulation of cellular metabolism [ 8 , 9 , 10 , 11 ], it is crucial to determine whether the antitumor activity of particular tyrosine kinase inhibitors (TKIs) is related to their effect at a given metabolic level. (biomedcentral.com)
  • In this review, we summarize and discuss principal metabolic changes following administration of particular kinase inhibitors on different levels of cellular metabolism (key metabolites and molecules affected by TKIs in cancer are summarized in Table 1 ). (biomedcentral.com)
  • Many lipid compounds or their metabolites can act as second messengers to regulate cellular functions and influence cell growth and apoptosis. (creative-proteomics.com)
  • Phosphoinositide phospholipase C performs its catalytic function at the plasma membrane where the substrate PIP2 is present. (wikipedia.org)
  • It is important to note that research has also discovered that, in addition to the plasma membrane, phosphoinositide phospholipase C also exists within other sub-cellular regions such as the cytoplasm and nucleus of the cell. (wikipedia.org)
  • Thus, OCRL represses the activity of oxysterol-binding protein-related protein 4L to prevent excessive PI(4,5)P2 hydrolysis by phosphoinositide phospholipase C ß3 and uncontrolled Ca2+ release from the endoplasmic reticulum. (bvsalud.org)
  • Arabidopsis AtPLC2 Is a Primary Phosphoinositide-Specific Phospholipase C in Phosphoinositide Metabolism and the Endoplasmic Reticulum Stress Response. (lipidall.com)
  • miRNAs act as regulatory factors for lipid metabolism and trafficking through associated enzymes and have been implicated in tumor cell proliferation and progression [ 11 ]. (biomedcentral.com)
  • This localization forecasts novel regulatory interfaces between neutral lipid metabolism and phosphoinositide signaling. (tamu.edu)
  • In a recent publication, our research group investigated the importance of a small class of regulatory lipids, the phosphoinositides (PPIns), for the support of myelination in peripheral nerves (1). (nih.gov)
  • Furthermore, in lipid droplets, the phosphorylation of HSL and Plin1 and the levels of catalytic and regulatory subunits of PKA were increased by glucocorticoids in wild-type mice. (nih.gov)
  • Three of the -OH groups (labeled red) can be phosphorylated in various combinations, giving rise to the seven different phosphoinositides (PPIns). (nih.gov)
  • The dysregulation of these signals in tumor cells leads to multiple cellular changes including alterations in DNA synthesis lipid metabolism cellular morphology cell adhesion properties and gene expression. (ecologicalsgardens.com)
  • Here, PI4P replaces the released specific lipid cargo within the lipid transfer protein preventing its backward transport. (nih.gov)
  • Glucocorticoid-induced lipolysis requires the phosphorylation of cytosolic hormone-sensitive lipase (HSL) and perilipin 1 (Plin1) in the lipid droplet by protein kinase A (PKA). (nih.gov)
  • A study by White et al (2009) found that psychosine's cytotoxic effects on oligodendroglia and Schwann cells was mediated through disruption of the architecture and composition of lipid rafts (cell membrane regions characterized by high cholesterol and sphingolipid concentration), followed by altered protein kinase C (PKC) function. (medscape.com)
  • 18. DRAM1 regulates autophagy and cell proliferation via inhibition of the phosphoinositide 3-kinase-Akt-mTOR-ribosomal protein S6 pathway. (nih.gov)
  • A mutation in the lipid-binding pocket of Ypt35p that reduces lipid binding markedly does not affect these PX domain protein interactions, arguing that lipid binding uses a different interaction surface than protein binding. (embl.de)
  • PHF treatment significantly maintained the glycemic state, antioxidant status, lipid profile, hepatic-architecture, and ultrastructural alterations in diabetic rats. (phcog.com)
  • 15] Psychosine was found to accumulate preferentially in white matter, with associated regional cholesterol increases causing alterations of lipid raft (LR) markers flotillin-2 and caveolin-1. (medscape.com)
  • Extrapolation of this concept to other members of the Sec14 superfamily suggests a mechanism by which a comprehensive cohort of Sec14-like nanoreactors sense correspondingly diverse pools of lipid metabolites. (tamu.edu)
  • Arabidopsis lipins mediate eukaryotic pathway of lipid metabolism and cope critically with phosphate starvation. (lipidall.com)
  • When I came to the NIH in 1985 as a postdoctoral fellow in Kevin Catt s group at the Endocrinology and Reproduction Research Branch of NICHD, I continued to explore the increasing complexity of inositol lipid and phosphate metabolism and its connection to Ca 2+ signaling, using the AngII receptors as a model system. (nih.gov)
  • Modulating the levels of various lipids in different organ and subcellular compartments requires specific regulation of various lipid metabolizing enzymes. (grc.org)
  • This conference focuses on understanding how the structure, chemistry, and dynamic distribution and regulation of these enzymes modulate lipids to affect signaling and metabolism. (grc.org)
  • Since then, PPIns have been linked to almost every important cellular process, including conserved roles in vesicular trafficking, signal transduction, ion channel regulation, as well as, most recently, to the control of lipid transport between various subcellular compartments (3). (nih.gov)
  • Scherer, P.E. Adipose tissue: from lipid storage compartment to endocrine organ. (nature.com)
  • Thus, the inhibition of Pik3r1 in adipocytes could alleviate lipid disorders caused by excess glucocorticoid exposure. (nih.gov)
  • Currently, FGF21 has been treated as a therapeutic target of metabolism disorders [ 25 ]. (hindawi.com)
  • A variety of CNS-related diseases are closely related to lipid metabolism disorders, such as cerebral ischemia, vascular dementia (VD), and Alzheimer's disease. (creative-proteomics.com)
  • The Molecular and Cellular Biology of Lipids GRC is a premier, international scientific conference focused on advancing the frontiers of science through the presentation of cutting-edge and unpublished research, prioritizing time for discussion after each talk and fostering informal interactions among scientists of all career stages. (grc.org)
  • The 2023 Molecular and Cellular Biology of Lipids Gordon Research Conference and Seminar will provide a platform for scientists from various sub-disciplines of lipid biology, biochemistry, and biophysics to present and discuss their most recent discoveries that impact the field. (grc.org)
  • This GRC will be held in conjunction with the "Molecular and Cellular Biology of Lipids" Gordon Research Seminar (GRS). (grc.org)
  • Furthermore, both inhibition of Gαi/o signaling and siRNA knockdown of β-arrestin 1/2 significantly reduced FSH-induced lipid droplet accumulation, implying a role for a Gαi/o/β-arrestin complex in FSH functions in this cell type. (frontiersin.org)
  • Cheong WF, Wenk MR, Shui G. Comprehensive analysis of lipid composition in crude palm oil using multiple lipidomic approaches. (lipidall.com)
  • While chronic FSH did not alter cell viability, FSH was able to increase lipid droplet size. (frontiersin.org)
  • Tumor metabolism is a thrilling discipline that focuses on mechanisms used by cancer cells to earn crucial building blocks and energy to preserve growth and overcome resistance to various treatment modalities. (biomedcentral.com)
  • However, in which manner Legionella actively exploits PI lipids to benefit its infection is not well characterized. (rcsb.org)
  • The collective activities of these PI4Ks ensure that essential lipids such as cholesterol, ceramide, or phosphatidylserine (PS) are efficiently transported out from the ER and delivered to these respective organelles using distinct ORPs (6). (nih.gov)
  • A special group of cellular lipids, known as lipid messengers or bioactive lipids participates in signaling cascades in all organisms, from bacteria to mammals. (johnshopkins.edu)
  • I also ran a state-of-the-art lipidomic analysis that characterized 282 lipid species in samples with and without PI5P4K depletion. (europa.eu)
  • With the development of lipidomic analysis techniques and the in-depth study of lipid metabolism, it is increasingly recognized that many physiological diseases are closely related to abnormal lipid metabolism. (creative-proteomics.com)
  • Our research also focuses on the parallels between cancer metabolism and photoreceptor degenerative diseases. (dmei.org)
  • Research of cancer metabolism is an area that has gained attention in recent decades. (por-journal.com)
  • They are an important constituent of cells, as a storage material for energy in living organisms, and can also participate in various cellular activities including material transport, energy metabolism, and information transfer. (creative-proteomics.com)
  • The objective of this study was to investigate the effects of different degrees of maternal dietary energy restriction on lipid deposition in embryonic tissues during the medium laying period (37 to 39 weeks) in Arbor Acres (AA) broiler breeders. (animbiosci.org)
  • In mammals, other than adipose tissues, the brain is the richest lipid-containing organ. (nih.gov)
  • In a series of studies, my colleagues and I established that AngII receptors used the phosphoinositide-Ca 2+ signaling cascade in the adrenal, a result that was consistent with other labs findings on AngII receptors in other tissues. (nih.gov)
  • The diversity in both lipid type and distribution plethora is important to the various roles various lipids they play in these processes. (grc.org)
  • While the relative amount of PPIns lipids represent only a small fraction (2-6%) of the total PI, the seven distinct PPIns members show high membrane turnover rates and numerous human enzymes are dedicated to their formation as well as degradation. (nih.gov)
  • This technique, which was also developed and used in several other labs, has become a driving force in understanding the spatial and temporal aspects of inositol lipid signals. (nih.gov)
  • However, the notion that increased phosphoinositide turnover is an early signaling event in the stimulatory actions of certain hormones and growth factors that elevate cytoplasmic Ca 2+ concentration was beginning to emerge. (nih.gov)
  • Sfh3, one of five Sec14 homologs in yeast, exhibits several interesting functional features, including its unique localization to lipid particles and microsomes. (tamu.edu)
  • The generation of 4-hydroxynonenal, an electrophilic lipid peroxidation end product, in rabbit cornea organ cultures treated with UVB light and nitrogen mustard. (nih.gov)
  • 3. Heimerl S, Höring M, Kopczynski D , Sigruener A, Hart C, Burkhardt R, Black A, Ahrends R , Liebisch G. Quantification of bulk lipid species in human platelets and their thrombin-induced release. (lipidomics.at)
  • Our recent work showed that CD8 + T cells rewired their lipid metabolism upon activation and accumulate saturated phosphoinositides (PI), unlike unactivated T cells, which were rich in polyunsaturated PI. (unibas.ch)