A5100396687- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Ubiquitin and proteasome pathways
- Lipid metabolism and biosynthesis
- 14-3-3 protein interactions
- Protein Kinase Regulation and GTPase Signaling
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- RNA modifications and cancer
- Cellular transport and secretion
- Liver Disease Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
- Receptor Mechanisms and Signaling
- Obstructive Sleep Apnea Research
- Growth Hormone and Insulin-like Growth Factors
- Caveolin-1 and cellular processes
- Biomedical Text Mining and Ontologies
- ATP Synthase and ATPases Research
- Neuroscience of respiration and sleep
- Cardiovascular Function and Risk Factors
- Diet and metabolism studies
- RNA and protein synthesis mechanisms
- Gut microbiota and health
- Cardiac electrophysiology and arrhythmias
Model Animal Research Center
2016-2025
Nanjing Drum Tower Hospital
2018-2025
Nanjing University
2015-2025
Fuyang Second People's Hospital
2025
Yunnan University of Traditional Chinese Medicine
2025
Anhui Medical University
2025
State Key Laboratory of Pharmaceutical Biotechnology
2015-2024
Fuyang City People's Hospital
2024
Central South University
2024
Jinan Central Hospital
2024
Abstract Fatty acids (FAs) are essential nutrients, but how they transported into cells remains unclear. Here, we show that FAs trigger caveolae-dependent CD36 internalization, which in turn delivers adipocytes. During the process, binding of to activates its downstream kinase LYN, phosphorylates DHHC5, palmitoyl acyltransferase CD36, at Tyr91 and inactivates it. then gets depalmitoylated by APT1 recruits another tyrosine SYK phosphorylate JNK VAVs initiate endocytic uptake FAs. Blocking...
Fatty acid uptake is the first step in fatty utilization, but it remains unclear how process regulated. Protein palmitoylation a acyl modification that plays key regulatory role protein targeting and trafficking; however, its function regulating metabolism unknown. Here, we show two of Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferases, DHHC4 DHHC5, regulate uptake. DHHC5 at different subcellular localizations to control palmitoylation, plasma membrane localization, activity...
AS160 (Akt substrate of 160 kDa) mediates insulin-stimulated GLUT4 (glucose transporter 4) translocation, but is widely expressed in insulin-insensitive tissues lacking GLUT4. Having isolated by 14-3-3-affinity chromatography, we found that binding to 14-3-3 isoforms HEK (human embryonic kidney)-293 cells was induced IGF-1 (insulin-like growth factor-1), EGF (epidermal factor), PMA and, a lesser extent, AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside). AS160-14-3-3 interactions...
TBC1D1 is a Rab-GTPase-activating protein (GAP) known to be phosphorylated in response insulin, growth factors, pharmacological agonists that activate 5'-AMP-activated kinase (AMPK), and muscle contraction. Silencing L6 cells by siRNA increases insulin-stimulated GLUT4 translocation, overexpression of 3T3-L1 adipocytes with low endogenous expression inhibits suggesting role regulating translocation. Aiming unravel the regulation during contraction potential AMPK intact skeletal muscle, we...
AS160 has emerged as a key player in insulin-mediated glucose transport through controlling GLUT4 trafficking, which is thought to be regulated by insulin-stimulated phosphorylation of sites including the 14-3-3 binding phospho-Thr649 (equivalent Thr642 human AS160). To define physiological roles AS160-Thr649 and homeostasis, we substituted this residue nonphosphorylatable alanine knockin mutation mice. The mutant protein was expressed at normal levels, while 14-3-3s abolished homozygous...
AS160 (Akt substrate of 160 kDa) is a Rab GTPase-activating protein implicated in insulin control GLUT4 (glucose transporter 4) trafficking. In humans, truncation mutation (R363X) one allele decreased the expression and caused severe postprandial hyperinsulinaemia during puberty. To complement limited studies possible we generated an AS160-knockout mouse. wild-type mice, relatively high adipose tissue soleus muscle, low EDL (extensor digitorum longus) muscle detectable liver only after...
Hundreds of candidate 14-3-3-binding (phospho)proteins have been reported in publications that describe one interaction at a time, as well high-throughput 14-3-3-affinity and mass spectrometry-based studies. Here, we transcribed these data into common format, deposited the collated from low-throughput studies MINT (http://mint.bio.uniroma2.it/mint), compared low- VisANT graphs are easy to analyze extend. Exploring prompted questions about technical biological specificity, which were...
Histone H3 lysine 27 trimethylation (H3K27me3) catalyzed by the enzymatic subunit EZH2 in Polycomb repressive complex 2 (PRC2) is essential for cells to ‘memorize’ gene expression patterns through cell divisions and plays an important role establishing maintaining identity during development. However, how epigenetic mark inherited generations remains poorly understood. Recently, we others demonstrate that CDK1 CDK2 phosphorylate at threonine 350 (T350) T350 phosphorylation binding of PRC2...
Significance Excess energy intake and physical inactivity are two major factors causing obesity, but the underlying mechanisms have not been fully understood. Both excess increase cellular status that is monitored by energy-sensing AMP-activated protein kinase (AMPK). We demonstrate AMPK–tre-2/USP6, BUB2, cdc16 domain family member 1 (the TBC GTPase activating domain) (TBC1D1) signaling nexus regulates insulin-like growth factor (IGF1) secretion. Disruption of this AMPK–TBC1D1 in mice...
SPEG (Striated muscle preferentially expressed protein kinase) has 2 kinase-domains and is critical for cardiac development function. However, it not clear how these function to maintain performance.To determine the molecular functions of SPEG.A proteomics approach identified SERCA2a (sarcoplasmic/endoplasmic reticulum calcium ATPase 2a) as a interacting with second kinase-domain but first SPEG. Furthermore, could phosphorylate Thr484 on SERCA2a, promote its oligomerization increase reuptake...
Abstract Congenital scoliosis (CS) is a complex genetic disorder characterized by vertebral malformations. The precise etiology of CS not fully defined. Here, we identify that mutation in dual serine/threonine and tyrosine protein kinase ( dstyk ) lead to CS-like malformations zebrafish. We demonstrate the mutants related wavy malformed notochord sheath formation abnormal axial skeleton segmentation due dysregulated biogenesis vacuoles function. Further studies show DSTYK located late...
Abstract Diabetic cardiomyopathy is a progressive disease in diabetic patients, and myocardial insulin resistance contributes to its pathogenesis through incompletely-defined mechanisms. Striated muscle preferentially expressed protein kinase (SPEG) has two kinase-domains critical cardiac regulator. Here we show that SPEG phosphorylated on Ser 2461 /Ser 2462 /Thr 2463 by B (PKB) response insulin. PKB-mediated phosphorylation of activates second kinase-domain, which turn phosphorylates...
The AS160 (Akt substrate of 160 kDa) is a Rab-GTPase activating protein (RabGAP) with several other functional domains, and its deficiency in mice or human patients lowers GLUT4 levels causes severe insulin resistance. How diminished proteins remains unknown. We found that the deletion decreased cell/tissue-autonomous manner. Consequently, skeletal muscle–specific caused postprandial hyperglycemia hyperinsulinemia. pathogenic effects are mainly, if not exclusively, due to loss RabGAP...
Abstract AGPATs (1-acylglycerol-3-phosphate O -acyltransferases) catalyze the acylation of lysophosphatidic acid to form phosphatidic (PA), a key step in glycerol-3-phosphate pathway for synthesis phospholipids and triacylglycerols. AGPAT2 is only AGPAT isoform whose loss-of-function mutations cause severe human congenital generalized lipodystrophy. Paradoxically, deficiency known dramatically increase level its product, PA. Here, we find that impairs biogenesis growth lipid droplets. We...
Insulin signals through its receptor to recruit insulin substrates (IRS) and phosphatidylinositol 3-kinase (PI3K) the plasma membrane for production of phosphatidylinositol-3,4,5-trisphosphate (PIP3) from phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2], which consequently activates protein kinase B (PKB). How transduce into cytoplasm is not clearly understood. Here we show that liquid-liquid phase separation (LLPS) plays a critical role in spatiotemporal control signaling regulating...
Cohort selection for clinical trials is a key step research. We proposed hierarchical neural network to determine whether patient satisfied criteria or not.We designed (denoted as CNN-Highway-LSTM LSTM-Highway-LSTM) the track 1 of national natural language processing (NLP) challenge (n2c2) on cohort in 2018. The composed 5 components: (1) sentence representation using convolutional (CNN) long short-term memory (LSTM) network; (2) highway adjust information flow; (3) self-attention reweight...