Reaction of alpha 2-macroglobulin with plasmin increases binding of transforming growth factors-beta 1 and beta 2.
The binding of 125I-transforming growth factors-beta 1 and beta 2 (TGF-beta 1 and TGF-beta 2) to alpha 2-macroglobulin (alpha 2M) was studied before and after reaction with plasmin, thrombin, trypsin, or methylamine. Complex formation between TGF-beta and native or reacted forms of alpha 2M was demonstrated by non-denaturing polyacrylamide gel electrophoresis and autoradiography. Reaction of native alpha 2M with plasmin or methylamine markedly increased the binding of 125I-TGF-beta 1 and 125I-TGF-beta 2 to alpha 2M. The alpha 2M-plasmin/TGF-beta complexes were minimally dissociated by heparin. Reaction of alpha 2M with thrombin or trypsin reduced the binding of 125I-TGF-beta 1 and 125I-TGF-beta 2; the resulting complexes were readily dissociated by heparin. Complexes between TGF-beta 2 and native or reacted forms of alpha 2M were less dissociable by heparin than the equivalent complexes with TGF-beta 1. These studies demonstrate that the TGF-beta-binding activity of alpha 2M is significantly affected by plasmin, thrombin, trypsin and methylamine. Observations that alpha 2M-plasmin preferentially binds TGFs-beta suggest a mechanism by which alpha 2M may regulate availability of TGFs-beta to target cells in vivo.
LaMarre
J
J
Department of Pathology, University of Guelph, Canada.
Wollenberg
G K
GK
Gonias
S L
SL
Hayes
M A
MA
D001345:Autoradiography; D001667:Binding, Competitive; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases; D005341:Fibrinolysin / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008744:Methylamines / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014357:Trypsin / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000378:metabolism*
D007457:Iodine Radioisotopes; D008744:Methylamines; D016212:Transforming Growth Factor beta; D000511:alpha-Macroglobulins; D006493:Heparin; C027451:methylamine; D010450:Endopeptidases; D014357:Trypsin; D013917:Thrombin; D005341:Fibrinolysin