Regulation of colony-stimulating factor-induced human myelopoiesis by transforming growth factor-beta isoforms.
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.
Salzman
S A
SA
Marshfield Medical Research Foundation, WI 54449, USA.
Mazza
J J
JJ
Burmester
J K
JK
D000595:Amino Acid Sequence; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D003115:Colony-Stimulating Factors / Q000378:metabolism / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D038042:Myelopoiesis; D020033:Protein Isoforms; D017433:Protein Structure, Secondary; D012313:RNA / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3
D003115:Colony-Stimulating Factors; D016207:Cytokines; D020033:Protein Isoforms; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor