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

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

Stable Identifier

R-HSA-177107

Type

Reaction [transition]

Species

Homo sapiens

Compartment

Golgi lumen, extracellular region

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

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

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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