Differential inhibition of transforming growth factor beta 1 and beta 2 activity by alpha 2-macroglobulin.
Affinity labeling and immunoprecipitation studies demonstrate that alpha 2-macroglobulin (alpha 2M) is the major serum-binding protein for transforming growth factors beta 1 and beta 2 (TGF-beta 1 and TGF-beta 2). Purified alpha 2M inhibits the binding of both 125I-TGF-beta 1 and 125I-TGF-beta 2 to cell surface receptors at I50 values of 200 and 10 micrograms/ml, respectively. alpha 2M (200 micrograms/ml) does not block TGF-beta 1 inhibition of CCL-64 mink lung cell growth but reduces this activity of TGF-beta 2 10-fold. The electrophoretic migration of 125I-TGF-beta.alpha 2M complexes on polyacrylamide gels under nondenaturing conditions demonstrates that alpha 2M has 10-fold greater affinity for TGF-beta 2 than for TGF-beta 1. Each of these complexes comigrates as a single band with the fast form of alpha 2M. We suggest that alpha 2M is an important differential regulator of the biological activities of TGF-beta 1 and TGF-beta 2 in vivo.
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892.
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Danielpour
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Sporn
D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007124:Immunoenzyme Techniques; D007700:Kinetics; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000378:metabolism / Q000494:pharmacology*
D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D000511:alpha-Macroglobulins; D015291:Transforming Growth Factors