Secretion and activation of the latent large complex of TGF-beta-1

Stable Identifier
R-HSA-177107
Type
Reaction [BlackBoxEvent]
Species
Homo sapiens
Compartment
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The large latent complex (LLC) of TGF-beta-1 (TGFB1) is secreted by exocytosis to the extracellular region. TGF-beta-1 in the LLC (called small latent TGF-beta complex (SCL)) 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, plasmin or other proteases 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 (Annes et al. 2003, Keski-Oja et al. 2004).

Literature References
PubMed ID Title Journal Year
12482908 Making sense of latent TGFbeta activation

Annes, JP, Rifkin, DB, Munger, JS

J Cell Sci 2003
15564041 TGF-beta activation by traction?

von Melchner, H, Keski-Oja, J, Koli, K

Trends Cell Biol 2004
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