Latent TGFβ complexes are transglutaminase cross-linked to fibrillin to facilitate TGFβ activation.

ABSTRACT: TGFβ superfamily members are potent growth factors in the extracellular matrix with essential roles in all aspects of cellular behaviour. Latent TGFβ binding proteins (LTBPs) are co-expressed with TGFβ, essential for correct folding and secretion of the growth factor, to form large latent complexes. These large latent complexes bind extracellular proteins such as fibrillin for sequestration of TGFβ in the matrix, essential for normal tissue function, and dysregulated TGFβ signalling is a hallmark of many fibrillinopathies. Transglutaminase-2 (TG2) cross-linking of LTBPs is known to play a role in TGFβ activation but the underlying molecular mechanisms are not resolved. Here we show that fibrillin is a matrix substrate for TG2 and that TG2 cross-linked complexes can be formed between fibril

SUBMITTER: Lockhart-Cairns MP 

PROVIDER: S-EPMC8932414 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature