A5088996594- Protein Kinase Regulation and GTPase Signaling
- Receptor Mechanisms and Signaling
- Renal Diseases and Glomerulopathies
- Mitochondrial Function and Pathology
- Ion channel regulation and function
- Pancreatic function and diabetes
- Platelet Disorders and Treatments
- Biotin and Related Studies
- Cell death mechanisms and regulation
- Metabolism, Diabetes, and Cancer
- Amino Acid Enzymes and Metabolism
- Cellular transport and secretion
- Chronic Kidney Disease and Diabetes
- ATP Synthase and ATPases Research
Nationwide Children's Hospital
2023-2024
Purdue University West Lafayette
2020-2022
Background Chronic kidney disease (CKD) is a leading cause of death, its progression driven by glomerular podocyte injury and loss, manifesting as proteinuria. Proteinuria includes loss coagulation zymogens, cofactors, inhibitors resulting in hypercoagulable state characterized enhanced thrombin generation. Both CKD proteinuria significantly increase the risk thromboembolic disease. Meanwhile, anticoagulant medications (which antagonize thereby prevent thromboembolism) have been shown to...
Abstract Phospholipase C ε (PLC ) generates lipid-derived second messengers at the plasma and perinuclear membranes in cardiovascular system. It is activated response to a wide variety of signals, such as those conveyed by Rap1A Ras, through mechanism that involves its C-terminal Ras association (RA) domains (RA1 RA2). However, complexity size PLC has hindered structural functional analysis. Herein, we report 2.7 Å crystal structure minimal fragment retains basal activity. This includes RA1...
Phospholipase Cε (PLCε) increases intracellular Ca
Phospholipase Cε (PLCε) cleaves phosphatidylinositol lipids to increase intracellular Ca
<b>Abstract ID 23793</b> <b>Poster Board 164</b> G protein-coupled receptors (GPCRs) transduce extracellular stimuli into intracellular signaling events through activation of the heterotrimeric protein subunits, Gα and Gβγ. proteins in turn activate effector enzymes, such as phospholipase C β (PLCβ), to produce second messengers. The four human PLCβ isoforms (PLCb1-4) are all potently activated by direct binding Gα<sub>q</sub>, but only PLCβ1-3 also directly Dysregulation...
<b>Abstract ID 24765</b> <b>Poster Board 85</b> Cardiovascular disease remains the leading cause of death worldwide, and phospholipase Ce (PLCe) is one players implicated in these pathways. Once activated downstream G protein-coupled receptors receptor tyrosine kinases, PLCe hydrolyzes membrane phosphoinositide lipids to produce inositol phosphates diacylglycerol. These secondary messengers allow release intracellular calcium stores activation pro-inflammatory pathways via protein kinase C....
<b>Abstract ID 24997</b> <b>Poster Board 83</b> Phospholipase C β (PLCβ) plays an important role in cardiovascular diseases and opioid analgesia. PLCβ catalyzes the hydrolysis of inner membrane lipid into two crucial secondary messengers, phosphatidylinositol-4,5-bisphosphate (PIP<sub>2</sub>) to inositol-1,4,5-triphosphate (IP<sub>3</sub>) diacylglycerol (DAG), which activate multiple signaling pathways modulate cellular behavior. is activated downstream G-protein coupled receptors (GPCRs)...
ABSTRACT Chronic kidney disease (CKD) is a leading cause of death, and its progression driven by glomerular podocyte injury loss, manifesting as proteinuria. Proteinuria includes urinary loss coagulation zymogens, cofactors, inhibitors. Importantly, both CKD proteinuria significantly increase the risk thromboembolic disease. Prior studies demonstrated that anticoagulants reduced in rats thrombin injured cultured podocytes. Herein we aimed to directly determine influence circulating...
G protein-coupled receptors (GPCRs) regulate diverse physiological processes in health and disease through activation of the heterotrimeric protein subunits, Gα Gβγ. proteins turn activate effector enzymes, such as phospholipase C β (PLCβ), to produce second messengers. The PLCβ subfamily has modest basal activity which is robustly increased by direct binding Gαq . PLCβ1-3 are also directly activated hydrolyzes phosphatidylinositol-4,5-bisphosphate (PIP2 ) generate diacylglycerol (DAG)...
Phospholipase C β (PLCβ) plays an important role in cardiovascular diseases and opioid analgesia. PLCβ catalyzes the hydrolysis of inner membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP2 ) to inositol-1,4,5-triphosphate (IP3 diacylglycerol (DAG). IP3 DAG are crucial secondary messengers that activate multiple signaling pathways modulate gene expression control responses extracellular signals. is a downstream effector G-protein coupled receptors (GPCRs) activated by both Gαq Gβγ...
Cardiovascular disease is the leading cause of death in world. The phospholipase C (PLC) family enzymes, particular PLCε subfamily, are essential for normal cardiovascular function. hydrolyzes phosphatidylinositol phosphates at cellular membranes, producing inositol (IPx ) and diacylglycerol (DAG). These crucial secondary messengers activate multiple downstream pathways, including cardiac contractility expression hypertrophic genes. In system, regulated through direct interactions with RhoA...
PLC (phospholipase C) enzymes hydrolyze phosphatidylinositol lipids to generate inositol phosphates (IPx ) and diacylglycerol (DAG). These second messengers stimulate intracellular calcium release protein kinase C activation. PLCε is the most recently identified member of family, activated downstream G protein-coupled receptors (GPCRs) receptor tyrosine kinases (RTKs) through direct interactions with proteins. In cardiovascular system, necessary for normal cardiac contractility, its...
Cardiovascular disease is the leading cause of death in United States. The phospholipase C (PLC) family enzymes catalyzes hydrolysis inner membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP2) to inositol-1,4,5-triphosphate (IP3) and diacylglycerol (DAG). IP3 DAG are crucial secondary messengers that activate multiple signaling pathways modulate gene expression control cellular function behavior. PLCe subfamily required for normal cardiovascular function, where it regulated through...
Phospholipase C (PLC) ε enzymes hydrolyze phosphatidylinositol lipids at cellular membranes to produce inositol phosphates (IPx) and diacylglycerol. These second messengers increase intracellular Ca2+ activate protein kinase C, allowing PLCε contribute numerous processes in response G protein-coupled receptor tyrosine activation. However, aberrant activity leads cardiac hypertrophy upregulation of oncogenic inflammatory signaling pathways. shares a conserved core with other PLC enzymes, but...