T Cell Ig and Mucin Domain-1-Mediated T Cell Activation Requires Recruitment and Activation of Phosphoinositide 3-Kinase
| Autor: | Jean S. Oak, Rosemarie H. DeKruyff, Anjali J. de Souza, Lawrence P. Kane, Ryan Jordanhazy, David A. Fruman |
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| Rok vydání: | 2008 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte CD4-Positive T-Lymphocytes T cell Immunology Enzyme-Linked Immunosorbent Assay Lymphocyte Activation Transfection Article Jurkat Cells Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound Antigens CD medicine Animals Humans Immunology and Allergy Lectins C-Type Hepatitis A Virus Cellular Receptor 1 Phosphorylation Tyrosine PI3K/AKT/mTOR pathway Mice Knockout Membrane Glycoproteins Phosphoinositide 3-kinase biology Effector Tyrosine phosphorylation Flow Cytometry Molecular biology Transmembrane protein Cell biology medicine.anatomical_structure chemistry biology.protein Interleukin-2 Receptors Virus Signal Transduction |
| Zdroj: | The Journal of Immunology. 180:6518-6526 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Ligation of the transmembrane protein T cell Ig and mucin domain (Tim)-1 can costimulate T cell activation. Agonistic Abs to Tim-1 are also capable of inducing T cell activation without additional stimuli. However, little is known about the biochemical mechanisms underlying T cell stimulation or costimulation through Tim-1. We show that a tyrosine in Tim-1 becomes phosphorylated in a lck-dependent manner, whereupon it can directly recruit p85 adaptor subunits of PI3K. This results in PI3K activation, which is required for Tim-1 function. We also provide genetic evidence that p85 expression is required for optimal Tim-1 function. Thus, we describe a pathway from Tim-1 tyrosine phosphorylation to the PI3K signaling pathway, which appears to be a major effector of Tim-1-mediated T cell activation. |
| Databáze: | OpenAIRE |
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