A5025074515- Protein Kinase Regulation and GTPase Signaling
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Advanced Proteomics Techniques and Applications
- Glycosylation and Glycoproteins Research
- Epigenetics and DNA Methylation
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 detection and testing
- Cancer-related gene regulation
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Biosensors and Analytical Detection
- Bioinformatics and Genomic Networks
- Hippo pathway signaling and YAP/TAZ
- Genomics and Chromatin Dynamics
- Long-Term Effects of COVID-19
- Birth, Development, and Health
- PI3K/AKT/mTOR signaling in cancer
- Gestational Diabetes Research and Management
- Pregnancy and preeclampsia studies
- Erythrocyte Function and Pathophysiology
- Signaling Pathways in Disease
- 14-3-3 protein interactions
- Melanoma and MAPK Pathways
Western University
2015-2024
Helmholtz Zentrum München
2024
Medical Research Institute
2015
University of Toronto
2010
China Agricultural University
2010
The University of Texas MD Anderson Cancer Center
2010
Cellular functions require specific protein-protein interactions that are often mediated by modular domains use binding pockets to engage particular sequence motifs in their partners. Yet, how different members of a domain family select for distinct is not fully understood. The human genome encodes 120 Src homology 2 (SH2) (in 110 proteins), which mediate proteins with diverse phosphotyrosine (pTyr)-containing sequences. structure the SH2 BRDG1 bound peptide revealed pocket was blocked loop...
Engineered SH2 domains with high affinity for phosphorylated tyrosine inhibit cell signaling downstream of receptor kinases.
The epithelial growth factor receptor plays an important role in cell migration and cancer metastasis, but the underlying molecular mechanism is not fully understood. We show here that differential regulation of rhodopsin-GTPase-activating (Rho-GAP) activity deleted liver 1 (DLC1) by tensin3 COOH-terminal tensin-like protein (cten) controls EGF-driven transformation. Tensin3 binds DLC1 through its actin-binding domain, a region missing cten, thereby releases autoinhibitory interaction...
BACKGROUND. The role of humoral immunity in COVID-19 is not fully understood, owing, large part, to the complexity antibodies produced response SARS-CoV-2 infection. There a pressing need for serology tests assess patient-specific antibody and predict clinical outcome.
Abstract Although cell migration plays a central role in development and disease, the underlying molecular mechanism is not fully understood. Here we report that phosphorylation-mediated switch comprising deleted liver cancer 1 (DLC1), tensin-3 (TNS3), phosphatase tensin homologue (PTEN) phosphoinositide-3-kinase (PI3K) controls spatiotemporal activation of small GTPases, Rac1 RhoA, thereby initiating directional induced by growth factors. On epidermal factor (EGF) or platelet-derived (PDGF)...
Objective To investigate the placental proteome differences between pregnant women complicated with gestational diabetes mellitus (GDM) and those normal glucose tolerance (NGT). Methods We used two-dimensional electrophoresis (2DE) to separate compare protein levels from GDM NGT groups. Differentially expressed proteins two groups were identified by MALDI-TOF/TOF mass spectrometry further confirmed Western blotting. The mRNA of related measured realtime RT-PCR. Immunohistochemistry (IHC) was...
An important issue in epigenetic research is to understand how the numerous methylation marks associated with histone and certain nonhistone proteins are recognized interpreted by hundreds of chromatin-binding modules (CBMs) a cell control chromatin state, gene expression, other cellular functions. We have assembled peptide chip that represents known putative lysine on histones p53 probed for binding group CBMs obtain comprehensive interaction network mediated methylation. Interactions...
Cells of the immune system communicate with their environment through immunoreceptors. These receptors often harbor intracellular tyrosine residues, which, when phosphorylated upon receptor activation, serve as docking sites to recruit downstream signaling proteins containing Src Homology 2 (SH2) domain. A systematic investigation interactions between SH2 domain and immunoreceptor tyrosine-based regulatory motifs (ITRM), including inhibitory (ITIM), activating (ITAM), or switching (ITSM)...
Deleted-in-liver cancer 1 (DLC1) exerts its tumor suppressive function mainly through the Rho-GTPase-activating protein (RhoGAP) domain. When activated, domain promotes hydrolysis of RhoA-GTP, leading to reduced cell migration. DLC1 is kept in an inactive state by intramolecular interaction between RhoGAP and sterile α motif (SAM) We have shown previously that this autoinhibited may be alleviated tensin-3 (TNS3) or PTEN. show here TNS3/PTEN-DLC1 interactions are mediated C2 domains former...
Abstract Motivation: Predicting protein interactions involving peptide recognition domains is essential for understanding the many important biological processes they mediate. It to consider binding strength of these help us construct more biologically relevant interaction networks that cellular context and competition between potential binders. Results: We developed a novel regression framework considers both positive (quantitative) negative (qualitative) data available mouse PDZ...
Src homology 2 (SH2) domains play a critical role in signal transduction mammalian cells by binding to phosphorylated Tyr (pTyr). Apart from few isolated cases viruses, no functional SH2 domain has been identified date prokaryotes. Here we identify 93 Legionella that are distinct sequence and specificity domains. The bacterial not only capable of proteins or peptides phosphorylation-dependent manner, some bind pTyr itself with micromolar affinities, property observed for feature the fold...
We have developed a rapid, accurate, and cost-effective serologic test for SARS-CoV-2 virus, which caused the COVID-19 pandemic, on basis of antibody-dependent agglutination antigen-coated latex particles. When validated using plasma samples that are positive or negative SARS-CoV-2, assay detected antibodies against receptor-binding domain spike (S-RBD) nucleocapsid protein with 100% specificity ∼98% sensitivity. Furthermore, we found strength S-RBD antibody response measured by correlated...
Abstract Background High abundance protein depletion is a major challenge in the study of serum/plasma proteomics. Prior to this study, most commercially available kits for highly abundant proteins had only been tested and evaluated adult serum/plasma, while efficiency on umbilical cord not clarified. Structural differences between some fetal (such as albumin) make it likely that approaches will be variable. Therefore, primary purposes present are investigate efficiencies several...
Src homology 2 (SH2) domains play an essential role in cellular signal transduction by binding to proteins phosphorylated on Tyr residue. Although phosphorylation (pY) is a prerequisite for essentially all SH2 characterized date, different prefer specific sequence motifs C-terminal the pY Because adopt same structural fold, it not well understood how have acquired ability recognize distinct motifs. We shown previously that EF and BG loops connect secondary structure elements domain dictate...
Melanoma is a malignant tumor with high misdiagnosis rate and poor prognosis. The bio-targeted therapy prevailing method in the treatment of melanoma; however, accompanying drug resistance inevitable. SH2 superbinder, triple-mutant Src Homology 2 (SH2) domain, shows potent antitumor ability by replacing natural SH2-containing proteins blocking multiple pY-based signaling pathways. Polyarginine (Arg)9, powerful vector for intracellular delivery large molecules, could transport therapeutic...
A basic but critical step in targeted proteomics by mass spectrometry is the separation of proteins from complex mixture whole proteome affinity purification. The bait protein usually immobilized on surface a solid support to enable affinity-based purification proteome. Here, we developed site-specific covalent immobilization through affinity-guided coupling (AGCC) single cysteine residue an SH2 domain (utilized as tag for target) with engineered ligand peptide. Site-specific...
NUMB is an evolutionarily conserved protein that plays important role in cell adhesion, migration, polarity, and fate determination. It has also been shown to play a the pathogenesis of certain cancers, although it remains controversial whether functions as oncoprotein or tumor suppressor. Here, we show binds anaplastic lymphoma kinase (ALK), receptor tyrosine aberrantly activated several forms cancer, this interaction regulates endocytosis activity ALK. Intriguingly, function NUMB-ALK...
Cellular functions are frequently regulated by protein-protein interactions involving the binding of a modular domain in one protein to specific peptide sequence another. This mechanism may be explored identify partners for proteins harboring peptide-recognition domain. Here we report proteomic strategy combining and microarray screening with biochemical cellular assays domain-mediated systematic manner. We applied this Numb, multi-functional containing phosphotyrosine-binding (PTB) Through...
SARS-CoV-2 infection triggers extensive host immune reactions, leading to severe diseases in certain individuals. However, the molecular basis underlying excessive yet non-productive responses COVID-19 remains incompletely understood. In this study, we conducted a comprehensive analysis of peripheral blood mononuclear cell (PBMC) proteome and phosphoproteome sepsis patients positive or negative for infection, as well healthy subjects, using quantitative mass spectrometry. Our findings...
Abstract Aim: To investigate the relationship between maternal overweight and fetal insulin resistance. Material Methods: Nineteen 30 lean pregnant women were recruited in present study. Maternal resistance determined by measuring sex hormone binding globulin (SHBG) concentrations venous or umbilical cord serum, respectively. age, gestational height, pre‐gravidity weight, pre‐partum as well gender, birth head circumference collected clinical data. Results: Fetuses of mothers had larger...
Protein complexes mediated by various post-translational modifications (PTMs) play important roles in almost every aspect of biological processes. PTM-mediated protein often have weak and transient binding properties, which limit their unbiased profiling especially complex samples. Here, we developed a plug-and-play chemical proteomic approach for high-throughput analyis complexes. Taking advantage the glutathione-S-transferase (GST) tag, is gold standard purification has wide access to...