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

Stable Identifier
R-HSA-177107
Type
Reaction [transition]
Species
Homo sapiens
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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 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.

Literature References
PubMed ID Title Journal Year
15564041 TGF-beta activation by traction?

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

Trends Cell Biol 2004
12482908 Making sense of latent TGFbeta activation

Annes, JP, Munger, JS, Rifkin, DB

J Cell Sci 2003
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