A5050836076- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Protein Tyrosine Phosphatases
- Cytokine Signaling Pathways and Interactions
- Signaling Pathways in Disease
- Chronic Lymphocytic Leukemia Research
- Galectins and Cancer Biology
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Immune Response and Inflammation
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- NF-κB Signaling Pathways
- Protein Kinase Regulation and GTPase Signaling
- Immunodeficiency and Autoimmune Disorders
- Mast cells and histamine
- Nuclear Receptors and Signaling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Bioactive Compounds and Antitumor Agents
- Lymphoma Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- interferon and immune responses
University of California, San Francisco
2016-2025
Howard Hughes Medical Institute
2014-2023
Rheumatology Research Center
2015-2022
Center for Rheumatology
1987-2013
University of California San Francisco Medical Center
2011
City College of San Francisco
2011
Immunovaccine (Canada)
2009
Institute of Biomedical Science
2009
Bipar
1998-2009
University of California, San Diego
2002-2004
The course of chronic lymphocytic leukemia (CLL) is variable. In aggressive disease, the CLL cells usually express an unmutated immunoglobulin heavy-chain variable-region gene (IgVH ) and 70-kD zeta-associated protein (ZAP-70), whereas in indolent mutated IgVH but lack expression ZAP-70.
The T cell antigen receptor (TCR) initiates signals by interacting with cytoplasmic protein tyrosine kinases (PTKs) through a 17-residue sequence motif [called the recognition activation (ARAM)] that is contained in TCRζ and CD3 chains. TCR stimulation induces phosphorylation of several cellular substrates, including ARAMs. Lck kinase activity required for two conserved residues an ARAM. This leads to recruitment second PTK, ZAP-70, both ZAP-70 Src homology 2 domains its phosphorylation....
The mechanism by which cell surface molecules regulate T production of lymphokines is poorly understood. Production interleukin-2 (IL-2) can be regulated signal transduction pathways distinct from those induced the antigen receptor. Stimulation CD28, a molecule expressed on most human cells, formation protein complex that bound to site IL-2 gene previously described binding sites and increased enhancer activity fivefold. CD28-responsive between -164 -154 base pairs transcription start site....
The human T cell leukemia Jurkat was used as a model to examine the requirements of activation. These studies demonstrated that antibodies reactive with cell-specific T3 antigen were insufficient result in activation cells, determined by secretion IL 2. 2 production occurred only presence second stimulus, phorbol ester PMA. With use an 2-specific cDNA probe, appearance RNA, similarly, when cells stimulated both anti-T3 and results demonstrate two-stimulus requirement for gene expression cells.
A homozygous mutation in the kinase domain of ZAP-70, a T cell receptor-associated protein tyrosine kinase, produced distinctive form human severe combined immunodeficiency. Manifestations this disorder included profound immunodeficiency, absence peripheral CD8+ cells, and abundant CD4+ cells that were refractory to receptor-mediated activation. These findings demonstrate ZAP-70 is essential for function suggest depend on different intracellular signaling pathways support their development...
The association between T3 and the T cell antigen receptor was examined using bearing leukemic line Jurkat. A monoclonal antibody, C305, produced, which reacted with idiotypic-like determinants expressed on molecule this antibody a disulfide-linked heterodimer of 90 kD, composed polypeptides 42 54 kD. Thus, C305 characteristics putative described by others. series mutants Jurkat, induced ethyl methane sulfonate or radiation, selected for negativity. In every instance, there concomitant loss...
Protein tyrosine kinases (PTKs) play an integral role in T cell activation and differentiation. Defects the Src-family PTKs mice lines have resulted variable defects thymic development antigen receptor (TCR) signal transduction. Here, three siblings are described with autosomal recessive form of severe combined immunodeficiency disease (SCID) which ZAP-70, a non-Src PTK, is absent as result mutations ZAP-70 gene. This absence associated TCR transduction, suggesting important functional for ZAP-70.
Abstract The human T cell leukemia Jurkat was used as a model to examine the requirements of activation. These studies demonstrated that antibodies reactive with cell-specific T3 antigen were insufficient result in activation cells, determined by secretion IL 2. 2 production occurred only presence second stimulus, phorbol ester PMA. With use an 2-specific cDNA probe, appearance RNA, similarly, when cells stimulated both anti-T3 and results demonstrate two-stimulus requirement for gene...
Stimulation of the T-cell antigen receptor (TCR) leads to tyrosine phosphorylation a number cellular proteins, including phospholipase C (PLC) gamma 1 and TCR zeta chain. We describe here 70-kDa phosphoprotein (ZAP-70) that associates with within 15 sec following stimulation. The ZAP-70 its association is independent other chains since stimulation functional CD8/zeta chimeric in TCR-negative T cell coprecipitation protein. In Jurkat expressing protein, occurs exclusively stimulated complex....
Activation of nonreceptor protein tyrosine kinases (PTKs) is essential for T cell receptor (TCR) responsiveness; however, the function individual PTK substrates often uncertain. A mutant line was isolated that lacked expression SLP-76 (SH2 domain–containing leukocyte 76 kilodaltons), a hematopoietically expressed adaptor and substrate. not required TCR-induced phosphorylation most proteins, but optimal activation phospholipase C-γ1 (PLC-γ1), as well Ras pathway activation. TCR-inducible gene...