Title : Association of the small latent transforming growth
factor-beta with
an eight cysteine repeat cysteine repeat of its binding
protein LTBP-1
Abstract :
- Transforming growth factor-betas ( TGF-betas ) are produced by most cells in large latent complexes of TGF-beta and its propeptide ( LAP ) associated with a binding protein
- The latent TGF-beta binding proteins ( LTBPs-1, -2 and -3 ) mediate the secretion and, subsequently, the association of latent TGF-beta complexes with the extracellular matrix ( ECM )
- The association of beta1- LAP with LTBP-1 was characterized at the molecular level with an expression system in mammalian cells, where TGF-beta1 and various fragments of LTBP-1 were co-expressed and secreted with the aid of a signal peptide synthesized to the LTBP-1 constructs
- Immunoblotting of the fusion protein complexes indicated that the third 8-Cys repeat Cys repeat of LTBP-1 bound covalently to the LAP region of TGF-beta1
- The cysteine required for the association between LTBP-1 and beta1- LAP was mapped to Cys33 of beta1- LAP
- The N-terminal region of LTBP-1 consisting of the first 400 amino acids was found to associate covalently with the ECM
- The data indicate that an 8-Cys repeat Cys repeat of LTBP is capable of covalent and specific protein- protein interactions
- These interactions are mediated by exchanging cysteine disulfide bonds between the core 8-Cys repeat Cys repeat and an optionally associated protein during the secretion
- This is, to our knowledge, the first demonstration of an extracellular protein module that is able to exchange cysteine disulfide bonds with heterologous ligand proteins