Nef and signal transduction Authored: Gillespie, ME, 2007-07-25 19:42:36 GENE ONTOLOGYGO:0050690 Nef interferes with cellular signal transduction pathways in a number of ways. Nef is associated with lipid rafts through its amino-terminal myristoylation and a proline-rich SH3-binding domain. These cholesterol-rich membrane microdomains appear to concentrate potent signaling mediators. Nef was found to complex with and activate serine/threonine protein kinase PAK-2, which may contribute to activation of infected cells. In vitro, HIV-infected T cells produce enhanced levels of interleukin-2 during activation. When expressed in macrophages, Nef intersects the CD40L signaling pathway inducing secretion of chemokines and other factors that attract resting T cells and promote their infection by HIV. Pubmed10618429 Pubmed12853962 Pubmed8570619 Reactome Database ID Release 43164944 Reactome, http://www.reactome.org ReactomeREACT_11068 Reviewed: Skowronski, J, 2007-08-07 14:33:41 PathwayStep3645 PathwayStep3644 PathwayStep3643 PathwayStep3642 PathwayStep3641 Nef Binds and activates the Src-family tyrosine kinase Lck Nef Binds and activates the Src-family tyrosine kinase Fyn 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 Nef Binds and activates the Src-family tyrosine kinase Hck Nef mediated activation of the T-cell receptor