Lec 3- Signaling Biochemistry Consequences of TCR signaling? -clonal expansion (secrete IL2; cell division) - effector functions (secrete cytokines-Th; killer func activated-CTLs) Big Picture: TCR signal=> …. => Gene expression alterations General Principle: Initial step in signal transduction is ligand induced dimerization (clustering) Phosphorylation=dynamic, reversible way of modulation protein function Kinase=enzyme that attaché phosphate groups to specific AA of proteins (Y, S, T) How TCR transducer signals with small tail?? •help of CD3 complex (its ITAMs) ITAMs: “immune tyrosine activation motif” -essential for TCR signaling -(YXXI/L-XXXXXX-YXXI/L) 2 SH2 domains -tyrosine phosphorylated = activation SH2 domains: bind to specific phosphotyrosinated protein domains PTK: Protein Tyrosine Kinases (initial TCR signaling) =>Src family – fyn, lck (SH3; SH2; Kinase with inhib + stim regulatory Y) =>Syk family – zap 70 (SH2; Sh2; Kinase with 1 reg Y) Regulating PTK activity -Csk = inhibits PTK (phos inhib Y)
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