Structure of the regulatory domains of the Src-family tyrosine kinase Lck

摘要: THE kinase p56lck (Lck) is a T-lymphocyte-specific member of the Src family non-receptor tyrosine kinases1. Members each contain unique amino-terminal regions, followed by Src-homology domains SH3 and SH2, domain. SH2 mediate critical protein interactions in many signal-transducing pathways2. They are small, independently folded modules about 60 100 residues, respectively, they often but not always found together same molecule. Like all nine Src-family kinases (reviewed ref. 3), Lck regulated phosphorylation short C-terminal tail its catalytic domain4. There evidence that binding phosphorylated to domain inhibits activity domain5,6 may act effect this regulation7. Here we report crystal structures for fragment bearing domains, alone complex with phosphotyrosyl peptide containing sequence regulatory tail. The latter represents apparatus Lck. SH3–SH2 forms similar dimers both crystals, binds at intermolecular SH3/SH2 contact. two show how an might recognize specific target suggest dimerization could play role regulating kinases.