Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation

摘要: Regulation through phosphorylation is a characteristic of signalling pathways and the lymphocyte kinase Lck (p56lck) both performs affected by it. Src-family tyrosine expressed in T lymphocytes, where it participates cellular immune response. Like all Src homologues, comprises SH3, SH2 domains. associates its distinctive amino-terminal segment with cytoplasmic tails either T-cell co-receptor, CD4 or CD8-alpha. Activated phosphorylates receptor zeta-chains, which then recruit ZAP70 to promote activation. activated autophosphorylation at Tyr 394 activation loop inactive when 505 near carboxy terminus phosphorylated interacts own domain. Here we report crystal structure domain (LCKK) state 1.7 A resolution. The reveals how phosphoryl group generates competent active site. Comparisons other structures indicate that phophophorylation ligand binding may general elicit two distinct hinge-like movements between subdomains. From modelling studies, suggest basis for inhibition 505.