Role for carbohydrate structures in TGF-beta 1 latency.
Transforming growth factor-beta (TGF-beta) (reviewed in refs 1-3) is a family of molecules that are made up as disulphide-bonded dimers of at least three different types of homologous polypeptides. The active molecules are cleaved from the C termini of precursors. TGF-beta 1, like other forms of TGF-beta, is synthesized and secreted in a latent high relative molecular mass form (L-TGF-beta 1) from which active TGF-beta 1 can be released by transient and probably unphysiological acidification. The latent complex from human platelets contains one dimeric TGF-beta 1 molecules, which is noncovalently associated with a disulphide-bonded complex of one dimeric remnant of the precursor and a single molecule of the so-called TGF-beta 1 binding protein (TGF-beta 1-BP). We report here that enzymatic removal in vitro of the carbohydrate structures in the remnant of the TGF-beta 1 precursor produces biologically active TGF-beta 1 from the latent complex, suggesting that carbohydrate structures are of importance in rendering TGF-beta 1 inactive in the complex in vivo.
Miyazono
K
K
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Heldin
C H
CH
D000818:Animals; D002241:Carbohydrates; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006026:Glycoside Hydrolases / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D009439:Neuraminidase / Q000494:pharmacology; D011498:Protein Precursors; D011506:Proteins; D051381:Rats; D013552:Swine; D016212:Transforming Growth Factor beta; D015291:Transforming Growth Factors
D002241:Carbohydrates; D011498:Protein Precursors; D011506:Proteins; D016212:Transforming Growth Factor beta; D015291:Transforming Growth Factors; D006026:Glycoside Hydrolases; D009439:Neuraminidase; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase