A5027212562- Adipose Tissue and Metabolism
- Regulation of Appetite and Obesity
- Liver Disease Diagnosis and Treatment
- Pancreatic function and diabetes
- Cytokine Signaling Pathways and Interactions
- Adipokines, Inflammation, and Metabolic Diseases
- Biochemical Analysis and Sensing Techniques
- Endoplasmic Reticulum Stress and Disease
- NF-κB Signaling Pathways
- Metabolism, Diabetes, and Cancer
- Liver physiology and pathology
- Protein Kinase Regulation and GTPase Signaling
- Growth Hormone and Insulin-like Growth Factors
- Peroxisome Proliferator-Activated Receptors
- Neurobiology and Insect Physiology Research
- Lipid metabolism and biosynthesis
- Retinoids in leukemia and cellular processes
- Diet, Metabolism, and Disease
- Cholesterol and Lipid Metabolism
- Protein Tyrosine Phosphatases
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- interferon and immune responses
- Exercise and Physiological Responses
University of Michigan
2016-2025
Laboratoire d’immunologie intégrative du cancer
2017-2022
Ann Arbor Center for Independent Living
2018-2020
Chubu University
2016
People's Hospital of Xinjiang Uygur Autonomous Region
2015
Michigan United
2014
Harvard University
2001-2014
Shanghai Institutes for Biological Sciences
2012
Chinese Academy of Sciences
2012
Michigan Medicine
2007
Inflammation associates with peripheral insulin resistance, which dysregulates nutrient homeostasis and leads to diabetes. induces the expression of SOCS proteins. We show that SOCS1 or SOCS3 targeted IRS1 IRS2, two critical signaling molecules for action, ubiquitin-mediated degradation. bound both recombinant endogenous IRS2 promoted their ubiquitination subsequent degradation in multiple cell types. Mutations conserved box abrogated its interaction elongin BC ubiquitin-ligase complex...
Serine/threonine phosphorylation of IRS-1 might inhibit insulin signaling, but the relevant sites are difficult to identify in cultured cells and validate isolated tissues. Recently, we discovered that recombinant NH2-terminal Jun kinase phosphorylates at Ser307, which inhibits insulin-stimulated tyrosine IRS-1. To monitor Ser307 various cell tissue backgrounds, prepared a phosphospecific polyclonal antibody designated αpSer307. This revealed TNF-α, IGF-1, or stimulated 3T3-L1 preadipocytes...
Insulin and insulin-like growth factor-1 (IGF-1) regulate metabolism body through homologous receptor tyrosine kinases that phosphorylate the insulin substrate (IRS) proteins. IRS-2 is an important IRS protein, as it mediates peripheral action β-cell survival. In this study, we show insulin, IGF-1, or osmotic stress promoted ubiquitin/proteasome-mediated degradation of in 3T3-L1 cells, Fao hepatoma, cells mouse embryo fibroblasts; however, insulin/IGF-1 did not promote IRS-1 preadipocytes...
SH2B1 (previously named SH2-B), a cytoplasmic adaptor protein, binds via its Src homology 2 (SH2) domain to variety of protein tyrosine kinases, including JAK2 and the insulin receptor. SH2B1-deficient mice are obese diabetic. Here we demonstrated that multiple isoforms (α, β, γ, and/or δ) were expressed in numerous tissues, brain, hypothalamus, liver, muscle, adipose tissue, heart, pancreas. Rat SH2B1β was specifically neural tissue SH2B1-transgenic (SH2B1Tg) mice. SH2B1Tg crossed with...
Hepatic steatosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and key component obesity-associated metabolic dysfunctions featuring dyslipidemia, insulin resistance, loss glycemic control. It has yet to be completely understood how much dysregulated de novo lipogenesis contributes the pathogenic development hepatic resistance. ATP-citrate lyase (ACL) lipogenic enzyme that catalyzes critical reaction linking cellular glucose catabolism lipogenesis, converting cytosolic citrate...
Src homology 2 B adapter protein 1 (SH2B1) modulates signaling by a variety of ligands that bind to receptor tyrosine kinases or JAK-associated cytokine receptors, including leptin, insulin, growth hormone (GH), and nerve factor (NGF). Targeted deletion Sh2b1 in mice results increased food intake, obesity, insulin resistance, with an intermediate phenotype seen heterozygous null on high-fat diet. We identified SH2B1 loss-of-function mutations large cohort patients severe early-onset obesity....
Major urinary protein (MUP) 1 is a lipocalin family member abundantly secreted into the circulation by liver. MUP1 binds to lipophilic pheromones and excreted in urine. Urinary MUP1/pheromone complexes mediate chemical communication rodents. However, it unclear whether circulatory has additional physiological functions. Here we show that regulates glucose lipid metabolism. expression was markedly reduced both genetic dietary fat-induced obesity diabetes. Mice were infected with adenoviruses...
The clock protein BMAL1 (brain and muscle Arnt-like 1) participates in circadian regulation of lipid metabolism, but its contribution to insulin AKT-regulated hepatic synthesis is unclear. Here we used both Bmal1(-/-) acute liver-specific Bmal1-depleted mice study the role refeeding-induced de novo lipogenesis liver. Both global deficiency depletion Bmal1 reduced lipogenic gene expression liver upon refeeding. Conversely, overexpression mouse by adenovirus was sufficient elevate levels mRNA...
Epidemiologic and animal studies implicate overconsumption of fructose in the development nonalcoholic fatty liver disease, but molecular mechanisms underlying fructose-induced chronic diseases remain largely unknown. Here, we have presented evidence supporting essential function lipogenic transcription factor carbohydrate response element-binding protein (ChREBP) mediating adaptive responses to protecting against hepatotoxicity. In WT mice, a high-fructose diet (HFrD) activated hepatic...
Abstract Microfold cells (M-cells) are specialized of the intestine that sample luminal microbiota and dietary antigens to educate immune intestinal lymphoid follicles. The function M-cells in systemic inflammatory responses still unclear. Here we show epithelial non-canonical NFkB signaling mediated by NFkB-inducing kinase (NIK) is highly active follicles, required for M-cell maintenance. Intestinal NIK modulates differentiation elicits both local IL-17A IgA production. Importantly, mouse...
Activation of the tyrosine kinase JAK2 is an essential step in cellular signaling by growth hormone (GH) and multiple other hormones cytokines. Murine has a total 49 tyrosines which, if phosphorylated, could serve as docking sites for Src homology 2 (SH2) or phosphotyrosine binding domain-containing molecules. Using yeast two-hybrid screen rat adipocyte cDNA library, we identified splicing variant SH2 protein SH2-B, designated SH2-Bbeta, JAK2-interacting protein. The carboxyl terminus...
Janus kinases (JAKs) are cytoplasmic tyrosine critical for signaling by growth hormone (GH) and many other ligands that bind to members of the cytokine receptor superfamily. SH2-Bβ was previously identified as a JAK2-interacting protein is tyrosyl phosphorylated in response GH cytokines activate JAK2. In this study, we examined whether alters activity SH2-Bβ, when coexpressed with JAK2, significantly increased phosphorylation JAK2 multiple cellular proteins stimulated kinase ≈20-fold....
Insulin regulates glucose homeostasis by binding and activating the insulin receptor, defects in responses (insulin resistance) induce type 2 diabetes.SH2-B, an Src homology (SH2) pleckstrin domain-containing adaptor protein, binds via its SH2 domain to receptor response insulin; however, physiological role remains unclear.Here we show that SH2-B was expressed liver, skeletal muscle, fat.Systemic deletion of impaired activation signaling fat, including tyrosine phosphorylation substrate 1...
Abstract Leptin controls body weight by activating its long form receptor (LEPRb). LEPRb binds to Janus kinase 2 (JAK2), a cytoplasmic tyrosine that mediates leptin signaling. We previously reported genetic deletion of SH2B1 (previously known as SH2-B), JAK2-binding protein, results in severe leptin-resistant and obese phenotypes, indicating is key endogenous positive regulator sensitivity. Here we show regulates signaling multiple mechanisms. In the absence leptin, constitutively bound, via...