CD28 Utilizes Vav-1 to Enhance TCR-Proximal Signaling and NF-AT Activation

• Published in: The Journal of immunology (1950) Vol. 165; no. 7; pp. 3820 - 3829
• Main Authors: Michel, Frederique, Mangino, Giorgio, Attal-Bonnefoy, Geraldine, Tuosto, Loretta, Alcover, Andres, Roumier, Anne, Olive, Daniel, Acuto, Oreste
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.10.2000
• Subjects: Adaptor Proteins, Signal Transducing; Adjuvants, Immunologic - metabolism; Adjuvants, Immunologic - physiology; CD28 antigen; CD28 Antigens - metabolism; CD28 Antigens - physiology; Cell Cycle Proteins; DNA-Binding Proteins - metabolism; Humans; Jurkat Cells; NF-AT protein; NFATC Transcription Factors; Nuclear Proteins; Phosphoproteins - biosynthesis; Phosphoproteins - metabolism; Phosphoproteins - physiology; Phosphorylation; Protein-Tyrosine Kinases - biosynthesis; Protein-Tyrosine Kinases - physiology; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-vav; Pseudopodia - immunology; Pseudopodia - metabolism; Receptors, Antigen, T-Cell, alpha-beta - physiology; Signal Transduction - immunology; SLP-76 protein; src Homology Domains - immunology; Transcription Factors - metabolism; Transfection; Vav-1 protein; ZAP-70 Protein-Tyrosine Kinase

The mechanism through which CD28 costimulation potentiates TCR-driven gene expression is still not clearly defined. Vav-1, an exchange factor for Rho GTPases thought to regulate, mainly through Rac-1, various signaling components leading to cytokine gene expression, is tyrosine phosphorylated upon C...