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Latent transforming growth factor-beta in serum. A specific complex with alpha 2-macroglobulin.
Open accessAbstract
The biological latency of serum transforming growth factor-beta (TGF-beta) was shown to be due to the interaction of TGF-beta with a specific serum binding protein. This binding protein was affinity labeled with 125I-TGF-beta, and its Mr and subunit structure were determined using sodium dodecyl sulfate-gel electrophoresis and gel filtration chromatography. Its Mr is reminiscent of that of the serum protease inhibitor, alpha 2-macroglobulin (alpha 2M). Immunoprecipitation of the 125I-TGF-beta-binding protein complex by a specific anti-alpha 2M antibody, and the formation of identical complexes between 125I-TGF-beta and purified alpha 2M, confirmed that alpha 2M is the TGF-beta-binding protein in serum. Immunoblot analysis showed that endogenous serum TGF-beta is also bound to alpha 2M. However, in contrast to added 125I-TGF-beta, the majority of the endogenous TGF-beta is linked to alpha 2M covalently. Alpha 2M and acid-activated TGF-beta co-eluted from a Superose 6 fast protein liquid chromatography column, confirming that the interaction of TGF-beta with alpha 2M accounts for the latency of serum TGF-beta. It is proposed that alpha 2M may serve an important multifunctional role at sites of inflammation by scavenging both active peptides and proteases that are released by platelets at the site of injury.
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Cites
Ignotz, R. A., & Massagué, J. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)35666-1 · Cited by 2,492
Cited by
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Roberts, A. B., & Sporn, M. B. (1990) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-49295-2_8 · Cited by 746
Transforming Growth Factor‐β: Major Role in Regulation of Extracellular Matrix
ROBERTS, A. B., HEINE, U. I., FLANDERS, K. C., & SPORN, M. B. (1990) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1990.tb17931.x · Cited by 696
Cytokine-mediated inflammation in acute lung injury
Goodman, R. B., Pugin, J., Lee, J. S., & Matthay, M. A. (2003) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(03)00059-5 · Cited by 688
The TGF-β family and its composite receptors
Massagué, J., Attisano, L., & Wrana, J. L. (1994) · Trends in Cell Biology · doi:10.1016/0962-8924(94)90202-x · Cited by 543
Common pathological processes in Alzheimer disease and type 2 diabetes: A review
Li, L., & Hölscher, C. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.09.001 · Cited by 367
Metadata
- Authors
- O'Connor-McCourt, M. D., & Wakefield, L. M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1987-10
- Volume
- 262
- Issue
- 29
- Pages
- 14090-14099
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1560768456
- Cited by
- 429
- References
- 1
- FWCI
- 11.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- O'Connor-McCourt, M. D., & Wakefield, L. M. (1987). Latent transforming growth factor-beta in serum. A specific complex with alpha 2-macroglobulin. Journal of Biological Chemistry. https://doi.org/10.1016/s0021-9258(18)47909-4
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.