Activation of the Src-family tyrosine kinase Hck by SH3 domain displacement

摘要: The protein Hck is a member of the Src family non-receptor tyrosine kinases which preferentially expressed in haematopoietic cells myeloid and B-lymphoid lineages. are inhibited by tyrosine-phosphorylation at carboxy-terminal site. SH2 domains these enzymes play an essential role this regulation binding to tyrosine-phosphorylated tail. crystal structure downregulated form has been determined reveals that domain regulates enzymatic activity indirectly; intramolecular interactions between SH3 catalytic appear stabilize inactive kinase. Here we compare roles modulating investigation C-terminally phosphorylated enzyme. We show addition HIV-1 Nef protein, high-affinity ligand for domain, either or activated causes large increase activity. intact SH3-binding motif crucial activation. Our results indicate more marked activation enzyme than does suggesting new mechanism kinases.