A5063233755- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Diabetes and associated disorders
- Immune Response and Inflammation
- Protein Tyrosine Phosphatases
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- Cell Adhesion Molecules Research
- Pancreatic function and diabetes
- Galectins and Cancer Biology
- Chronic Lymphocytic Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- interferon and immune responses
- Protein Kinase Regulation and GTPase Signaling
- Mast cells and histamine
- Cancer Immunotherapy and Biomarkers
- Diabetes Management and Research
- Cytokine Signaling Pathways and Interactions
- Complement system in diseases
- Cytomegalovirus and herpesvirus research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Systemic Lupus Erythematosus Research
University of Colorado Denver
2014-2023
University of Colorado Anschutz Medical Campus
2004-2023
National Jewish Health
2011-2020
University of Colorado Boulder
2020
University of North Carolina at Chapel Hill
1998-2018
American Thyroid Association
2017
Colorado State University
2016
University of Colorado Health
2003-2015
National Institute of Environmental Health Sciences
2009
National Institutes of Health
2009
Coligation of the Fc receptor on B cells, FcγRIIB1, with cell antigen (BCR) leads to abortive BCR signaling. Here it was shown that FcγRIIB1 recruits phosphotyrosine phosphatase PTP1C after coligation. This association is mediated by binding a 13-amino acid tyrosine-phosphorylated sequence carboxyl-terminal Src homology 2 domain and activates PTP1C. Inhibitory signaling recruitment are dependent presence tyrosine within sequence. deficient in motheaten mice which do not express functional...
Recent studies have demonstrated dramatic shifts in metabolic supply-and-demand ratios during inflammation, a process resulting localized tissue hypoxia within inflammatory lesions (“inflammatory hypoxia”). As part of the adaptive immune response, T cells are recruited to sites hypoxia. Given profound effects on gene regulation, we hypothesized that T-cell differentiation is controlled by To pursue this hypothesis, analyzed transcriptional consequences ambient (1% oxygen) broad panel...
Engagement of antigen receptor complexes induces rapid activation Src-family kinases and association with phosphatidylinositol-3' kinase (PI-3 kinase). Here it was found that the Src homology 3 (SH3) domain Lyn Fyn bound to a proline-rich region (residues 84 99) within 85-kilodalton subunit (p85) PI-3 kinase. The binding SH3 purified led five- sevenfold increase in specific activity Ligand-induced stimulation activated kinase, this blocked by peptide containing residues 99 p85. These data...
Although the best-defined function of type II major histocompatibility complex (MHC-II) is presentation antigenic peptides to T lymphocytes, these molecules can also transduce signals leading alternatively cell activation or apoptotic death. MHC-II a heterodimer two transmembrane proteins, each containing short cytoplasmic tail that dispensable for transduction death signals. This suggests an undefined MHC-II-associated transducer in signaling response. Here we describe novel plasma membrane...
Abstract Cyclic-di-GMP and cyclic-di-AMP are second messengers produced by bacteria influence bacterial cell survival, differentiation, colonization, biofilm formation, virulence, bacteria–host interactions. In this study, we show that in both RAW264.7 macrophage cells primary bone marrow-derived macrophages, the production of IFN-β IL-6, but not TNF, response to cyclic-di-GMP requires MPYS (also known as STING, MITA, TMEM173). Furthermore, expression was required for IFN factor 3 NF-κB...
Germinal centers (GCs) generate memory B and plasma cells, which are essential for long-lived humoral immunity. GC cells with high-affinity cell receptors (BCRs) selectively expanded. To enable this selection, BCRs of such thought to signal differently from those lower affinity. We show that, surprisingly, most proliferating did not demonstrate active BCR signaling. Rather, spontaneous induced signaling was limited by increased phosphatase activity. Accordingly, both SH2 domain-containing...
Abstract NK cells express cell surface receptors for MHC class I proteins (KIR). Engagement of these inhibits cytotoxic programs. KIR can be expressed on T cells, and their engagement also results in inhibition effector functions initiated by the CD3/TCR complex. While human genes belong to Ig gene superfamily, mouse a family dimeric lectins. Despite distinct evolutionary origins, we show here that both HLA-Cw3-specific p58.183 H-2D d/k-specific Ly49A recruit same protein tyrosine...
The B cell antigen receptor complex is a hetero-oligomeric structure composed of binding, membrane immunoglobulin, and transducer-transporter substructures. substructure disulfide-linked dimers immunoglobulin (Ig)-α Ig-β/γ subunits that are products the mb-1(α) B29 (β/γ) genes. Although associates with Src family kinases activated after ligation, site interaction these other cytoplasmic effector molecules unknown. tails Ig-α Ig-β chains were found to associate distinct sets molecules. chain...
The constitutive culture supernatant (SN) of the macrophage tumor line P388D1 (P388 SN) and concanavalin A (Con A)-induced T cell hybridoma FS6-14.13 (FS6 Con were shown to contain nonspecific factors capable inducing increased Ia expression by normal resting B cells in a dose-dependent manner. In six consecutive experiments relative increase induced P388 SN was 4.9 +/- 0.9, with FS6 10.7 1.5, combination both preparations 13.0 1.7. This observed occur virtually all cells, reaching maximum...
CD45 is a member of family membrane proteins that possess phosphotyrosine phosphatase activity, and the source much tyrosine activity in lymphocytes. In view its enzymatic high copy number, it seems likely functions transmembrane signal transduction by lymphocyte receptors are coupled to activation kinases. The B cell antigen receptor was found transduce Ca2+-mobilizing only if cells expressed CD45. Also, both immunoglobulin M (mIgM) were lost from surface treated with antibody CD45,...
To explore the mechanism(s) by which Syk protein tyrosine kinase participates in B cell antigen receptor (BCR) signaling, we have studied function of various mutants cells made deficient homologous recombination knockout. Both SH2 domains were required for BCR-mediated and phospholipase C (PLC)-gamma 2 phosphorylation, inositol 1,4,5-triphosphate release, Ca2+ mobilization. A possible explanation this requirement was provided findings that recruitment to tyrosine-phosphorylated...
Recent data implicating loss of PTP1C tyrosine phosphatase activity in the genesis multiple hemopoietic cell defects found systemic autoimmune/immunodeficient motheaten (me) and viable (mev) mice suggest that plays an important role modulating intracellular signaling events regulating activation differentiation. To begin elucidating for this cytosolic lymphoid signal transduction, we have examined early mitogenic responses induced by B antigen receptor (BCR) ligation me mev splenic cells...
Exposure of naïve B cells to the cytokine interleukin-4 (IL-4) and/or antigen leads a state “priming,” in which subsequent aggregation major histocompatibility complex class II molecules induces mobilization calcium ions and cell proliferation. However, it is not clear how critical this priming for immune responses or normally induced vivo. Injection mice with commonly used adjuvant alum led splenic accumulation spleen previously unknown population IL-4–producing, Gr1 + cells. These IL-4...