Endocytosis of TRAM Authored: Shamovsky, V, 2012-04-19 Edited: Shamovsky, V, 2012-05-25 Pubmed16757566 Pubmed18222170 Pubmed18297073 Reactome Database ID Release 432201341 Reactome, http://www.reactome.org ReactomeREACT_121217 Reviewed: D'Eustachio, P, 2012-05-25 Reviewed: Granucci, Francesca, Zanoni, Ivan, 2012-11-13 TRIF-related adapter molecule (TRAM) is a sorting adapter which recruits TRIF to activated TLR4. Like TLR4, TRAM was detected both at the plasma membrane and in the endosomal compartment. TRAM was reported to recruit TRIF to the plasma membrane [Tanimuro N et al 2008]. However, TRAM did not induce TRIF-mediated signaling from the cell surface, instead, TRAM endocytosis was required for activation of IRF3 and induction of IFN-beta [Tanimuro N et al 2008; Kagan JC et al 2008]. Although, endocytosis of both TLR4 and TRAM and their association are required to trigger TRIF-mediated signaling, TRAM can target endosomes independently on its interaction with TLR4. TRAM cellular localization is controlled by myristoylation and phosphorylation of its N-terminal bipartite sorting signal motif [Kagan JC et al 2008]. <p>TRAM has been shown to undergo phosphorylation on Ser-16 by protein kinase C epsilon in LPS-treated human THP1 and murine embryonic fibroblasts (MEF) cells [McGettrick AF et al 2006].