DOCK2:ELMO1:RAC1:Nef Complex myristoylated Nef Protein (numerous variants) Nef binds a ternary complex comprising DOCK2 guanine nucleotide exchange factor for small Rho-family GTPase Rac, its cofactor ELMO1, and Rac, and activates Rac through this interaction Pubmed14737186 Reactome Database ID Release 43200952 Reactome, http://www.reactome.org ReactomeREACT_11090 Reviewed: Skowronski, J, 2007-08-07 14:33:41 The infectious cycle of primate lentiviruses is intimately linked to interactions between cells of the immune system. Nef, a potent virulence factor, alters cellular environments to increase lentiviral replication in the host, functioning as an adaptor protein. Nef activates Rac in T cell lines and in primary T cells following infection with HIV-1 in the absence of antigenic stimuli. Nef activates Rac by binding the DOCK2-ELMO1 complex, and this interaction is linked to the abilities of Nef to inhibit chemotaxis and promote T cell activation. Nef targets a critical switch that regulates Rac GTPases downstream of chemokine- and antigen-initiated signaling pathways. This interaction enables Nef to influence multiple aspects of T cell function and thus provides an important mechanism by which Nef impacts pathogenesis by primate lentiviruses.