Thrombin inactivates acidic fibroblast growth factor but not basic fibroblast growth factor. Export

@article{citeulike:4190061, abstract = {Incubation of bovine brain derived acidic fibroblast growth factor (aFGF) with bovine or human thrombin, 0.5 NIH unit/mL, for 24 h at 37 degrees C results in cleavage of the mitogen, generating a 14-kilodalton fragment which has significantly reduced affinity for immobilized heparin as compared to aFGF, and is at least 50-fold less potent at stimulating mitogenesis. In addition, an 18 amino acid peptide, aFGF(123-140), is generated, identifying one of the thrombin cleavage sites as the Arg-122/Thr-123 bond. The peptide, aFGF(123-140), is neither mitogenic itself nor an inhibitor of the mitogenic activity of aFGF. The cleavage of aFGF by thrombin is inhibited by heparin (50 micrograms/mL) and is completely blocked by the irreversible thrombin inhibitors D-Phe-Pro-Arg chloromethyl ketone and hirudin. Incubation of aFGF with 50 units/mL thrombin at 37 degrees C results in rapid cleavage of the mitogen into several fragments. In contrast, incubation of bovine brain derived basic fibroblast growth factor with 1 unit/mL thrombin for 24 h, or 50 units/mL thrombin for 6 h, does not result in significant cleavage of mitogen. The results show that the C-terminal region of aFGF is of functional importance in both mitogenesis and heparin binding. Most importantly, a novel role for anionic heparin-binding growth factors and their fragments is indicated in physiologic and pathologic situations associated with thrombin generation.}, author = {Lobb, R. R.}, citeulike-article-id = {4190061}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/3382640}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=3382640}, day = {5}, issn = {0006-2960}, journal = {Biochemistry}, keywords = {culture, fgf, h, heparin\_culture}, month = {April}, number = {7}, pages = {2572--2578}, posted-at = {2009-03-17 23:43:23}, priority = {2}, title = {Thrombin inactivates acidic fibroblast growth factor but not basic fibroblast growth factor.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/3382640}, volume = {27}, year = {1988} }

TY - JOUR ID - citeulike:4190061 L3 - citeulike-article-id:4190061 N2 - Incubation of bovine brain derived acidic fibroblast growth factor (aFGF) with bovine or human thrombin, 0.5 NIH unit/mL, for 24 h at 37 degrees C results in cleavage of the mitogen, generating a 14-kilodalton fragment which has significantly reduced affinity for immobilized heparin as compared to aFGF, and is at least 50-fold less potent at stimulating mitogenesis. In addition, an 18 amino acid peptide, aFGF(123-140), is generated, identifying one of the thrombin cleavage sites as the Arg-122/Thr-123 bond. The peptide, aFGF(123-140), is neither mitogenic itself nor an inhibitor of the mitogenic activity of aFGF. The cleavage of aFGF by thrombin is inhibited by heparin (50 micrograms/mL) and is completely blocked by the irreversible thrombin inhibitors D-Phe-Pro-Arg chloromethyl ketone and hirudin. Incubation of aFGF with 50 units/mL thrombin at 37 degrees C results in rapid cleavage of the mitogen into several fragments. In contrast, incubation of bovine brain derived basic fibroblast growth factor with 1 unit/mL thrombin for 24 h, or 50 units/mL thrombin for 6 h, does not result in significant cleavage of mitogen. The results show that the C-terminal region of aFGF is of functional importance in both mitogenesis and heparin binding. Most importantly, a novel role for anionic heparin-binding growth factors and their fragments is indicated in physiologic and pathologic situations associated with thrombin generation. IS - 7 JF - Biochemistry SN - 0006-2960 EP - 2578 TI - Thrombin inactivates acidic fibroblast growth factor but not basic fibroblast growth factor. VL - 27 SP - 2572 KW - culture KW - fgf KW - h KW - heparin_culture AU - Lobb, RR PY - 1988/04/05/ UR - http://view.ncbi.nlm.nih.gov/pubmed/3382640 ER -