Regulation of colony-stimulating factor-induced human myelopoiesis by transforming growth factor-beta isoforms.

Abstract

Transforming growth factor-beta (TGF-beta) proteins are multifunctional regulators of cell growth and differentiation. The three isoforms, TGF-beta1, -beta2, -beta3 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-beta1 and TGF-beta2 had bimodal dose-dependent stimulatory and inhibitory effects on granulocyte-macrophage colony-stimulating factor induced Day 7 granulocyte-macrophage colony-forming units. The effects of TGF-beta3 were only inhibitory. At low concentrations, TGF-beta1 and -beta2 stimulated growth, whereas at higher concentrations both isoforms inhibited growth. We now report that TGF-beta1, TGF-beta2, and TGF-beta3 are similar to each other at low concentrations; at higher concentrations TGF-beta1 and TGF-beta3 inhibit growth, but TGF-beta2 stimulates growth. Our results are consistent with the known affinities of the TGF-beta isoforms with the Type II TGF-beta signaling receptor, which has greater affinity for TGF-beta1 and TGF-beta3 than TGF-beta2.