Lck:Nef myristoylated Nef Protein (numerous variants) Nef Binds and activates the Src-family tyrosine kinase Lck Authored: Gillespie, ME, 2007-07-25 19:42:36 Pubmed10544125 Pubmed7859737 Reactome Database ID Release 43200954 Reactome, http://www.reactome.org ReactomeREACT_11220 Reviewed: Skowronski, J, 2007-08-07 14:33:41 The Nef protein of the primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), is a myristylated protein associated with increased viral replication and enhanced pathogenicity. Both the potentiation of T-lymphocyte activation and the enhanced serine-phosphorylation of HIV-1 capsid by Nef correlate with increased viral replication. The Nef proteins from HIV-1 and SIV bind to Lck. The SH3 and SH2 domains of Lck are sufficient for coprecipitation with non-tyrosine-phosphorylated Nef proteins. The conserved core region of HIV-1 Nef is essential for the interaction with Lck and is also important for enhanced HIV-1 replication in T-lymphocytes. The SIV and HIV-1 Nef proteins are differentially tyrosine-phosphorylated. The kinase-active Lck tyrosine-phosphorylates SIVmac239 Nef but does not phosphorylate HIV-1 Nef.