Abstract
Transforming growth factor- g (TGF- g) proteins are multifunctional regulators of cell growth and differentiation. The three isoforms, TGF- g 1, - g 2, - g 3 share approximately 70% identical amino acid sequence and are coded by three distinct genes. Growth and differentiation functions in which the isoforms have differential activity include: inhibition of colorectal cancer cell growth, migration of aortic endothelial cells, survival of ciliary ganglionic neurons, and binding to cell surface receptors. A previous paper reported that TGF- g 1 and TGF- g 2 had bimodal dosedependent stimulatory and inhibitory effects on granulocyte-macrophage colony-stimulating factor induced Day 7 granulocyte-macrophage colony-forming units. The effects of TGF- g 3 were only inhibitory. At low concentrations, TGF- g 1 and - g 2 stimulated growth, whereas at higher concentrations both isoforms inhibited growth. We now report that TGF- g 1, TGF- g 2, and TGF- g 3 are similar to each other at low concentrations; at higher concentrations TGF- g 1 and TGF- g 3 inhibit growth, but TGF- g 2 stimulates growth. Our results are consistent with the known affinities of the TGF- g isoforms with the Type II TGF- g signaling receptor, which has greater affinity for TGF- g 1 and TGF- g 3 than TGF- g 2.