A5044593774- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Protein Tyrosine Phosphatases
- Cancer-related gene regulation
- T-cell and B-cell Immunology
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- HIV Research and Treatment
- MicroRNA in disease regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- RNA Research and Splicing
- Pharmacological Effects of Natural Compounds
- Cytomegalovirus and herpesvirus research
- RNA Interference and Gene Delivery
- HIV/AIDS drug development and treatment
- Bacteriophages and microbial interactions
- Erythrocyte Function and Pathophysiology
- Advanced biosensing and bioanalysis techniques
- Bacillus and Francisella bacterial research
University of California, San Diego
2011-2023
Moores Cancer Center
2001-2019
University of North Carolina at Chapel Hill
2019
Society for Immunotherapy of Cancer
2014
Vrije Universiteit Brussel
2011
St George's, University of London
2009
Center for Biologics Evaluation and Research
1992-1998
National Institutes of Health
1998
National Cancer Institute
1994-1997
United States Food and Drug Administration
1993-1996
Activation of early response genes by interferons (IFNs) requires tyrosine phosphorylation STAT (signal transducers and activators transcription) proteins. It was found that the serine-threonine kinase mitogen-activated protein (MAPK) [specifically, 42-kilodalton MAPK or extracellular signal-regulated 2 (ERK2)] interacted with α subunit IFN-α/β receptor in vitro vivo. Treatment cells IFN-β induced activation caused Stat1α to coimmunoprecipitate. Furthermore, expression dominant negative...
Upon interferon (IFN) stimulation, Stat1 becomes tyrosine phosphorylated and translocates into the nucleus, where it binds to DNA activate transcription.The activity of is dependent on phosphorylation, its inactivation in nucleus accomplished by a previously unknown protein phosphatase (PTP).We have now purified PTP from HeLa cell nuclear extract identified as TC45, isoform T-cell (TC-PTP).TC45 can dephosphorylate both vitro vivo.Nuclear extracts lacking TC45 fail Stat1.Furthermore,...
Interferon-α (IFN-α) and IFN-γ regulate gene expression by tyrosine phosphorylation of several transcription factors that have the 91-kilodalton (p91) protein interferon-stimulated factor-3 (ISGF-3) as a common component. Interferon-activated complexes bind enhancers present in promoters early response genes such high-affinity Fcγ receptor (FcγRI). Treatment human peripheral blood monocytes or basophils with interleukin-3 (IL-3), IL-5, IL-10, granulocyte-macrophage colony-stimulating factor...
Abstract Although type I IFNs play critical roles in antiviral and antitumor activity, it remains to be elucidated how are produced sterile conditions of the tumor microenvironment directly affect tumor-infiltrating immune cells. Mouse de novo gliomas show increased expression IFN messages, mice, CD11b+ brain-infiltrating leukocytes (BIL) main source that induced partially a STING (stimulator genes)-dependent manner. Consequently, glioma-bearing StingGt/Gt mice showed shorter survival lower...
Interferons (IFNs) induce early-response genes by stimulating Janus family (Jak) tyrosine kinases, leading to phosphorylation of Stat transcription factors. Previous studies implicated protein-tyrosine phosphatase (PTP) activity in the control IFN-regulated Jak/Stat signaling, but specific PTPs responsible remained unidentified. We have found that SH2 domain-containing PTP1 (SHPTP1; also called PTP1C, HCP, or SHP) reversibly associates with IFN-alpha receptor complex upon IFN addition....
Non-coding microRNAs (miRs) are a vital component of post-transcriptional modulation protein expression and, like coding mRNAs harbour oncogenic properties. However, the mechanisms governing miR and identity affected transcripts remain poorly understood. Here we identify inositol phosphatase SHIP1 as bonafide target miR-155. We demonstrate that in diffuse large B cell lymphoma (DLBCL) elevated levels miR-155, consequent diminished result autocrine stimulation by pro-inflammatory cytokine...
A variety of cytokines and growth factors act through an induction gene expression mediated by a family latent transcription called STAT (signal transducers activators transcription) proteins. Ligand-induced tyrosine phosphorylation the STATs promotes their homodimer heterodimer formation subsequent nuclear translocation. We demonstrate here that protein heterocomplexes exist prior to cytokine treatment. When unstimulated HeLa cells are ruptured in hypotonic buffer without salt or detergent,...
Using analytical and preparative methods, we demonstrated the presence of megaplasmids with molecular weight larger than 450 x 10(6) in two plant-associated bacteria Rhizobium meliloti Pseudomonas solanacearum. Such giant plasmids were found 8 9 P. solanacearum strains tested all 18 R. tested.
The epidermal growth factor (EGF) receptor activates several signaling cascades in response to the ligands EGF and amphiregulin (AR). One of these events involves tyrosine phosphorylation STATs (signal transducers activators transcription), a process believed require activation kinase JAK family. In this report we demonstrate that EGF- AR-induced STAT requires intrinsic activity but not presence Jak1. We show both wild type (WT) truncated receptors lacking all autophosphorylation sites...
Interferon establishes an antiviral state in numerous cell types through the induction of a set immediate-early response genes. Activation these genes is mediated by phosphorylation latent transcription factors STAT family. We found that infection primary foreskin fibroblasts with human cytomegalovirus (HCMV) causes selective transcriptional activation alpha/beta-interferon-responsive ISG54 gene. However, no or nuclear translocation proteins was detected. occurs independent protein synthesis...
Engagement of the IFN-alphabeta receptor initiates multiple signaling cascades, including activation STAT. In this study, we demonstrate that IFN-alphabeta, although antiproliferative in wild-type CD4(+) or CD8(+) T cells, act as strong mitogens on their STAT1(-/-) counterparts. Furthermore, exert little effect apoptosis but are potent survival factors absence STAT1. The antiapoptotic response STAT1 is predominantly mediated by STAT3, and to a lesser extent STAT5A/B. contrast, mitogenic...
Type I and II interferons (IFNs) exert opposing effects on the progression of multiple sclerosis, even though both IFNs use signal transducer activator transcription 1 (STAT1) as a signaling mediator. Here we report that STAT1-deficient mice expressing transgenic T cell receptor against myelin basic protein spontaneously develop experimental autoimmune encephalomyelitis with dramatically increased frequency. The heightened susceptibility to this disease appears be triggered by reduced number...
Toll-like receptor 4 (TLR4) is unique among the TLRs in its use of multiple adaptor proteins leading to activation both interferon regulatory factor 3 (IRF3) and nuclear κB (NF-κB) pathways. Previous work has demonstrated that TLR4 initiates NF-κB from plasma membrane, but subsequent translocation endosomes required for IRF3 activation. Here we have characterized several components signaling pathway governs We find phospholipase C γ2 (PLCγ2) accounts LPS-induced inositol 1,4,5-trisphosphate...
Abstract Background Several host-encoded antiviral factors suppress HIV-1 replication in a cell-autonomous fashion vitro . The relevance of these defenses to the control vivo remains be elucidated. We hypothesized that cellular restriction plays significant role observed suppression "elite controllers", individuals who maintain undetectable levels viremia absence antiretroviral therapy (ART). comprehensively compared expression 34 host and activation CD4+ T cells sorted cell subsets between...
Interferon-α (IFNα) can activate several members of the signal transducers and activator transcription (STAT) factor family, a process that requires tyrosine kinases Jak1 Tyk2. Here we provide evidence IFNα-mediated activation various STAT proteins is regulated by distinct mechanisms. Piceatannol, previously reported as Syk/ZAP70-specific kinase inhibitor, selectively inhibits phosphorylation STAT3 STAT5, but not STAT1 STAT2. This inhibition paralleled loss IFNAR1 in response to IFNα,...
Interferon regulatory factor 3 (IRF3) is known to participate in the transcriptional induction of interferon (IFN) α and IFNβ genes, as well a number interferon-stimulated genes (ISGs), result viral infection. In present study we demonstrate activation IRF3 followed by ISG after exposure cells bacterial cell wall component lipopolysaccharide. Engagement Toll-like receptors lipopolysaccharide triggered nuclear translocation IRF3, its DNA binding subsequent several interferon-regulated genes....