Identification of a Structural Domain That Distinguishes the Actions of the Type 1 and 2 Isoforms of Transforming Growth Factor β on Endothelial Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-07, Vol.89 (14), p.6290-6294
• Main Authors: Qian, Su Wen, Burmester, James K., Merwin, June R., Madri, Joseph A., Sporn, Michael B., Roberts, Anita B.
• Format: Article
• Language: English
• Subjects: Amino acids; Analytical, structural and metabolic biochemistry; Animals; Base Sequence; Biological and medical sciences; Cell Division - drug effects; Cell growth; Cell lines; Cell Movement - drug effects; Chimeras; Cloning, Molecular; Complementary DNA; domains; Endothelial cells; Endothelium, Vascular - cytology; Fundamental and applied biological sciences. Psychology; Growth Inhibitors; In Vitro Techniques; isoforms; Molecular Sequence Data; Molecules; Oligodeoxyribonucleotides - chemistry; Plasmids; Polymerase chain reaction; Protein hormones. Growth factors. Cytokines; Protein isoforms; Proteins; Recombinant Fusion Proteins - chemistry; Structure-Activity Relationship; structure-activity relationships; Transforming Growth Factor beta - chemistry; Transforming Growth Factor beta - pharmacology; transforming growth factor- beta
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.14.6290

A chimeric transforming growth factor β (TGF-β) molecule has been synthesized to map the amino acids responsible for the substantially greater activity of TGF-β1than TGF-β2on growth and migration of endothelial cells. This chimera consists of a dimer of a monomeric unit composed of amino acids 1-39 of TGF-β2, 40-82 of TGF-β1, and 83-112 of TGF-β2. Structural identity of the purified recombinant protein has been confirmed by immunoblotting and NH2-terminal sequencing. The biological potency of the TGF-β2-1-2chimera was equal to that of TGF-β1in inhibition of growth of both fetal bovine heart endothelial cells and rat epididymal fat pad microvascular endothelial cells. Similarly, the TGF-β2-1-2chimera was nearly equivalent to TGF-β1and at least 10-fold more active than TGF-β2in inhibiting migration of bovine aortic endothelial cells. These results identify the sequence between amino acids 40-82 as an important region within TGF-β that functions to specify a TGF-β1- or TGF-β2-like activity.