Hck-1:Nef myristoylated Nef Protein (numerous variants) Nef Binds and activates the Src-family tyrosine kinase Hck Authored: Gillespie, ME, 2007-07-25 19:42:36 Pubmed7859737 Pubmed8599760 Pubmed9024665 Reactome Database ID Release 43200858 Reactome, http://www.reactome.org ReactomeREACT_11224 Reviewed: Skowronski, J, 2007-08-07 14:33:41 The protein Hck is a member of the Src family of non-receptor tyrosine kinases which is preferentially expressed in haematopoietic cells of the myeloid and B-lymphoid lineages. Src kinases are inhibited by tyrosine-phosphorylation at a carboxy-terminal site. The SH2 domains of these enzymes play an essential role in this regulation by binding to the tyrosine-phosphorylated tail. The SH2 domain of Hck regulates enzymatic activity indirectly; intramolecular interactions between the SH3 and catalytic domains appear to stabilize an inactive form of the kinase. The HIV-1 Nef protein, which is a high-affinity ligand for the Hck SH3 domain, binds to either the downregulated or activated form of Hck causing a large increase in Hck catalytic activity. The intact SH3-binding motif in Nef is crucial for Hck activation.