Dimeric TGFB1 Large latent complex of TGFB1 Secretion and activation of the latent large complex of TGF-beta-1 Authored: Heldin, CH, Moustakas, A, Huminiecki, L, Jassal, B, 2006-02-02 Edited: Jassal, B, 2006-03-22 11:41:32 Pubmed12482908 Pubmed15564041 Reactome Database ID Release 43177107 Reactome, http://www.reactome.org ReactomeREACT_6888 Reviewed: Heldin, CH, 2006-04-18 14:26:12 Reviewed: Huang, Tao, 2012-05-14 The large latent complex (LLC) of TGF-beta-1 (TGFB1) is secreted by exocytosis to the extracellular region. TGF-beta-1 in the LLC cannot interact with the receptors and for this reason we say that it requires "activation". This means release from the LLC. This release is achieved by many mechanisms: proteolytic cleavage of the LTBPs, thrombospondin-1 binding to the LLC, integrin alphaV-beta6 binding to the LLC, reactive oxygen species and low pH. The release of mature dimeric TGF-beta-1 is essentially a mechanical process that demands cleavage and opening of the LLC structure so that the caged mature C-terminal TGF-beta-1 polypeptide is released to reach the receptor.