Bioactive TGF-beta can associate with lipoproteins and is enriched in those containing apolipoprotein E3.
Transforming growth factor-beta1 (TGF-beta1) has central functions in development, tissue maintenance, and repair and has been implicated in major diseases. We discovered that TGF-beta1 contains several amphipathic helices and hydrophobic domains similar to apolipoprotein E (apoE), a protein involved in lipoprotein metabolism. Indeed, TGF-beta1 associates with lipoproteins isolated from human plasma, cultured liver cells, or astrocytes, and its bioactivity was highest in high-density lipoprotein preparations. Importantly, lipoproteins containing the apoE3 isoform had higher TGF-beta levels and bioactivity than those containing apoE4, a major genetic risk factor for atherosclerosis and Alzheimer's disease. Because TGF-beta1 can be protective in these diseases an association with apoE3 may be beneficial. Association of TGF-beta with different types of lipoproteins may facilitate its diffusion, regulate signaling, and offer additional specificity for this important growth factor.
Tesseur
Ina
I
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
Zhang
Hui
H
Brecht
Walter
W
Corn
Jacob
J
Gong
Jian-Sheng
JS
Yanagisawa
Katsuhiko
K
Michikawa
Makoto
M
Weisgraber
Karl
K
Huang
Yadong
Y
Wyss-Coray
Tony
T
D000818:Animals; D053318:Apolipoprotein E3 / Q000235:genetics / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D008074:Lipoproteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000378:metabolism; D017433:Protein Structure, Secondary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D008074:Lipoproteins; D020033:Protein Isoforms; D053773:Transforming Growth Factor beta1