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GAP/NF-1

Transcription factors NFAT, NFkB, Oct-1, AP1, c-myc, nur77 etc.

Transcription factors NFAT, NFkB, Oct-1, AP1, c-myc, nur77 etc.

Gene expression

FIGURE 17-2 Simplified schematic representation of signal transduction events that occur in T cells following antigen recognition. Reproduced with permission from Kisielow, P. (1995). Apoptosis in intrathymic T-cell development. In "Apoptosis and the Immune Response" (C. D. Gregory, ed.), pp. 13-53. Wiley-Liss, New York.

initiated by the a/3 T-cell receptor. Tyrosine phosphorylation is called into play, which includes the ¿"-chain of the T-cell receptor complex. For reference, a diagrammatic representation of the T-cell receptor signal transduction is given in Figure 17-2. Phospholipase Cyi is also phosphorylated, reflecting the elevated activities of Fyn and Lck tyrosine kinases. The ¿"-chain of the T-cell receptor then associates with the ZAP-70 tyrosine kinase (Figure 17-2). Activation of phospholipase C leads to hydrolysis of phosphatidylinositol 4,5-biphos-phate (PIP2), generating 1,2-diacylglycerol (DAG) and inositol triphosphate (IP3), which lead to the activation of protein kinase C (PKC). Intracellular Ca2+ levels are increased by IP3. Potential PKC targets include p21ras, its GTPase activity controlling GAP and NF1 proteins, and raf and MAP kinases. Calcium increases activate calcineurin, a Ca2+ calmodulin-dependent protein phosphatase. NFAT, a transcriptional regulator of IL-2 gene expression, is a target of calcineurin that can activate NFAT by dephosphorylation. NF-kB and AP-1 can be targets of the T-cell receptor signal transduction pathway. Oct-1, c-myc, and nur 77 may also be involved.

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