Fibroblast growth factor 2 induced proliferation in osteoblasts and bone marrow stromal cells: A whole cell model

Biophysical Journal

Volumn 91, Issue 8, 2006, Pages 3097-3112

  Dupree, Melissa A ^a   Pollack, Solomon R ^a   Levine, Elliot M ^b   Laurencin, Cato T ^c  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b WISTAR INSTITUTE   (United States)

^c University of Virginia   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FIBROBLAST GROWTH FACTOR 2; PROTEOHEPARAN SULFATE;

ANIMAL CELL; ARTICLE; BINDING KINETICS; BONE MARROW; CELL KINETICS; CELL PROLIFERATION; CONTROLLED STUDY; ENDOCYTOSIS; IN VITRO STUDY; INTERNALIZATION; NONHUMAN; OSTEOBLAST; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN SECRETION; PROTEIN TRANSPORT; RABBIT; SIGNAL TRANSDUCTION; STOICHIOMETRY; STROMA CELL; WHOLE CELL;

EID: 33749509386     PISSN: 00063495     EISSN: None     Source Type: Journal    
DOI: 10.1529/biophysj.106.087098     Document Type: Article

References (107)

1. Muraglia, A., R. Cancedda, and R. Quarto. 2000. Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. J. Cell Sci. 113:1161-1166.
2. Bruder, S. P., N. Jaiswal, and S. E. Haynesworth. 1997. Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation. J. Cell. Biochem. 64:278-294.
3. Banfi, A., A. Muraglia, B. Dozin, M. Mastrogiacomo, R. Cancedda, and R. Quarto. 2000. Proliferation kinetics and differentiation potential of ex vivo expanded human bone marrow stromal cells: implications for their use in cell therapy. Exp. Hematol. 28:707-715.
4. von Knoch, F., C. Jaquiery, M. Kowalsky, S. Schaeren, C. Alabre, I. Martin, H. E. Rubash, and A. S. Shanbhag. 2005. Effects of bisphosphonates on proliferation and osteoblast differentiation of human bone marrow stromal cells. Biomaterials. 26:6941-6949.
5. Gori, F., T. Thomas, K. C. Hicok, T. C. Spelsberg, and B. L. Riggs. 1999. Differentiation of human marrow stromal precursor cells: bone morphogenetic protein-2 increases OSF2/CBFA1, enhances osteoblast commitment, and inhibits late adipocyte maturation. J. Bone Miner. Res. 14:1522-1535.
6. Liu, P., B. O. Oyajobi, R. G. G. Russell, and A. Scutt. 1999. Regulation of osteogenic differentiation of human bone marrow stromal cells: interaction between transforming growth factor-β and 1,25(OH)(2) vitamin D-3 in vitro. Calcif. Tissue Int. 65:173-180.
7. Martin, I., A. Muraglia, G. Campanile, R. Cancedda, and R. Quarto. 1997. Fibroblast growth factor-2 supports ex vivo expansion and maintenance of osteogenic precursors from human bone marrow. Endocrinology. 138:4456-4462.
8. Bianchi, G., A. Banfi, M. Mastrogiacomo, R. Notaro, L. Luzzatto, R. Cancedda, and R. Quarto. 2003. Ex vivo enrichment of mesenchymal cell progenitors by fibroblast growth factor 2. Exp. Cell Res. 287:98-105.
9. Bikfalvi, A., S. Klein, G. Pintucci, and D. B. Rifkin. 1997. Biological roles of fibroblast growth factor-2. Endocr. Rev. 18:26-45.
10. Gospodarowicz, D., N. Ferrara, L. Schweigerer, and G. Neufeld. 1987. Structural characterization and biological functions of fibroblast growth-factor. Endocr. Rev. 8:95-114.
11. Fannon, M., K. E. Forsten, and M. A. Nugent. 2000. Potentiation and inhibition of bFGF binding by heparin: a model for regulation of cellular response. Biochemistry. 39:1434-1445.
12. Dowd, C. J., C. L. Cooney, and M. A. Nugent. 1999. Heparan-sulfate mediates bFGF transport through basement membrane by diffusion with rapid reversible binding. J. Biol. Chem. 274:5236-5244.
13. Forsten, K. E., M. Fannon, and M. A. Nugent. 2000. Potential mechanisms for the regulation of growth factor binding by heparin. J. Theor. Biol. 205:215-230.
14. Padera, R., G. Venkataraman, D. Berry, R. Godavarti, and R. Sasisekharan. 1999. FGF-2/fibroblast growth factor receptor/heparin-like glycosaminoglycan interactions: a compensation model for FGF-2 signaling. FASEB J. 13:1677-1687.
15. Filion, R. J., and A. S. Popel. 2004. A reaction-diffusion model of basic fibroblast growth factor interactions with cell surface receptors. Ann. Biomed. Eng. 32:645-663.
16. Gopalakrishnan, M., K. Forsten-Williams, and U. C. Tauber. 2004. Ligand-induced coupling versus receptor pre-association: cellular automaton simulations of FGF-2 binding. J. Theor. Biol. 227:239-251.
17. Ibrahimi, O. A., F. M. Zhang, S. C. L. Hrstka, M. Mohammadi, and R. J. Linhardt. 2004. Kinetic model for FGF, FGFR, and proteoglycan signal transduction complex assembly. Biochemistry. 43:4724-4730.
18. Forsten-Williams, K., C. C. Chua, and M. A. Nugent. 2005. The kinetics of FGF-2 binding to heparan-sulfate proteoglycans and MAP kinase signaling. J. Theor. Biol. 233:483-499.
19. Jaye, M., J. Schlessinger, and C. A. Dionne. 1992. Fibroblast growth-factor receptor tyrosine kinases - molecular analysis and signal transduction. Biochim. Biophys. Acta. 1135:185-199.
20. Keresztes, M., and J. Boonstra. 1999. Import(ance) of growth factors in(to) the nucleus. J. Cell Biol. 145:421-424.
21. Florkiewicz, R. Z., A. Baird, and A. M. Gonzalez. 1991. Multiple forms of bFGF: differential nuclear and cell surface localization. Growth Factors. 4:265-275.
22. Arnaud, E., C. Touriol, C. Boutonnet, M. C. Gensac, S. Vagner, H. Prats, and A. C. Prats. 1999. A new 34-kiloDalton isoform of human fibroblast growth factor 2 is cap-dependently synthesized by using a non-AUG start codon and behaves as a survival factor. Mol. Cell. Biol. 19:505-514.
23. Rifkin, D. B., N. Quarto, P. Mignatti, J. Bizik, and D. Moscatelli. 1991. New observations on the intracellular-localization and release of BFGF. Ann. N. Y. Acad. Sci. 638:204-206.
24. Delrieu, I. 2000. The high molecular weight isoforms of basic fibroblast growth factor (FGF-2): an insight into an intracrine mechanism. FEBS Lett. 468:6-10.
25. Powers, C. J., S. W. McLeskey, and A. Wellstein. 2000. Fibroblast growth factors, their receptors and signaling. Endocr. Relat. Cancer. 7:165-197.
26. Sleeman, M., J. Fraser, M. McDonald, S. N. Yuan, D. White, P. Grandison, K. Kumble, J. D. Watson, and J. G. Murison. 2001. Identification of a new fibroblast growth factor receptor, FGFR5. Gene. 271:171-182.
27. Krufka, A., S. Guimond, and A. C. Rapraeger. 1996. Two hierarchies of FGF-2 signaling in heparin: mitogenic stimulation and high-affinity binding/receptor transphosphorylation. Biochemistry. 35:11131-11141.
28. Delehedde, M., M. Seve, N. Sergeant, I. Wartelle, M. Lyon, P. S. Rudland, and D. G. Fernig. 2000. Fibroblast growth factor-2 stimulation of p42/44(MAPK) phosphorylation and IκB degradation is regulated by heparan-sulfate/ heparin in rat mammary fibroblasts. J. Biol. Chem. 275:33905-33910.
29. Yayon, A., M. Klagsbrun, J. D. Esko, P. Leder, and D. M. Ornitz. 1991. Cell-surface, heparin-like molecules are required for binding of basic fibroblast growth-factor to its high-affinity receptor. Cell. 64:841-848.
30. Fannon, M., and M. A. Nugent. 1996. Basic fibroblast growth factor binds its receptors, is internalized, and stimulates DNA synthesis in Balb/c3T3 cells in the absence of heparan-sulfate. J. Biol. Chem. 271:17949-17956.
31. Dailey, L., D. Ambrosetti, A. Mansukhani, and C. Basilico. 2005. Mechanisms underlying differential responses to FGF signaling. Cytokine Growth Factor Rev. 16:233-247.
32. Klint, P., and L. Claesson-Welsh. 1999. Signal transduction by fibroblast growth factor receptors. Front. Biosci. 4:D165-D177.
33. Pages, G., P. Lenormand, G. Lallemain, J. C. Chambard, S. Meloche, and J. Pouyssegur. 1993. Mitogen-activated protein-kinases P42(MAPK) and P44(MAPK) are required for fibroblast proliferation. Proc. Natl. Acad. Sci. USA. 90:8319-8323.
34. Johnson, G. L., and R. Lapadat. 2002. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 298:1911-1912.
35. Schlessinger, J. 2000. Cell signaling by receptor tyrosine kinases. Cell. 103:211-225.
36. Kudla, A. J., N. C. Jones, R. S. Rosenthal, K. Arthur, K. L. Clase, and B. B. Olwin. 1998. The FGF receptor-1 tyrosine kinase domain regulates myogenesis but is not sufficient to stimulate proliferation. J. Cell Biol. 142:241-250.
37. 1 transition. Proc. Natl. Acad. Sci. USA. 84:6770-6774.
38. Bailly, K., F. Soulet, D. Leroy, F. Amalric, and G. Bouche. 2000. Uncoupling of cell proliferation and differentiation activities of basic fibroblast growth factor. FASEB J. 14:333-344.
39. Bossard, C., H. Laurell, L. Van den Berghe, S. Meunier, C. Zanibellato, and H. Prats. 2003. Translokin is an intracellular mediator of FGF-2 trafficking. Nat. Cell Biol. 5:433-439.
40. Davis, M. G., M. Zhou, S. Ali, J. D. Coffin, T. Doetschman, and G. W. Dorn. 1997. Intracrine and autocrine effects of basic fibroblast growth factor in vascular smooth muscle cells. J. Mol. Cell. Cardiol. 29:1061-1072.
41. Maher, P. A. 1996. Nuclear translocation of fibroblast growth factor (FGF) receptors in response to FGF-2. J. Cell Biol. 134:529-536.
42. Kilkenny, D. M., and D. J. Hill. 1996. Perinuclear localization of an intracellular binding protein related to the fibroblast growth factor (FGF) receptor 1 is temporally associated with the nuclear trafficking of FGF-2 in proliferating epiphyseal growth plate chondrocytes. Endocrinology. 137:5078-5089.
43. Benavente, C. A., W. D. Sierralta, P. A. Conget, and J. J. Minguell. 2003. Subcellular distribution and mitogenic effect of basic fibroblast growth factor in mesenchymal uncommitted stem cells. Growth Factors. 21:87-94.
44. Reilly, J. F., and P. A. Maher. 2001. Importin β-mediated nuclear import of fibroblast growth factor receptor: role in cell proliferation. J. Cell Biol. 152:1307-1312.
45. Hsia, E., T. P. Richardson, and M. A. Nugent. 2003. Nuclear localization of basic fibroblast growth factor is mediated by heparan-sulfate proteoglycans through protein kinase C signaling. J. Cell. Biochem. 88:1214-1225.
46. Amalric, F., G. Bouche, H. Bonnet, P. Brethenou, A. M. Roman, I. Truchet, and N. Quarto. 1994. Fibroblast growth factor-II (FGF-2) in the nucleus - translocation process and targets. Biochem. Pharmacol. 47:111-115.
47. Schlessinger, J., A. N. Plotnikov, O. A. Ibrahimi, A. V. Eliseenkova, B. K. Yeh, A. Yayon, R. J. Linhardt, and M. Mohammadi. 2000. Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization. Mol. Cell. 6:743-750.
48. Pellegrini, L., D. F. Burke, F. von Delft, B. Mulloy, and T. L. Blundell. 2000. Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin. Nature. 407:1029-1034.
49. Harmer, N. J., L. L. Ilag, B. Mulloy, L. Pellegrini, C. V. Robinson, and T. I. Blundell. 2004. Towards a resolution of the stoichiometry of the fibroblast growth factor (FGF)-FGIF receptor - Heparin complex. J. Mol. Biol. 339:821-834.
50. Pantoliano, M. W., R. A. Horlick, B. A. Springer, D. E. Vandyk, T. Tobery, D. R. Wetmore, J. D. Lear, A. T. Nahapetian, J. D. Bradley, and W. P. Sisk. 1994. Multivalent ligand-receptor binding interactions in the fibroblast growth-factor system produce a cooperative growth-factor and heparin mechanism for receptor dimerization. Biochemistry. 33:10229-10248.
51. McCarthy, T. L., M. Centrella, and E. Canalis. 1988. Further biochemical and molecular characterization of primary rat parietal bone cell-cultures. J. Bone Miner. Res. 3:401-408.
52. Canalis, E., M. Centrella, and T. McCarthy. 1988. Effects of basic fibroblast growth-factor on bone-formation in vitro. J. Clin. Invest. 81:1572-1577.
53. Scutt, A., and P. Bertram. 1999. Basic fibroblast growth factor in the presence of dexamethasone stimulates colony formation, expansion, and osteoblastic differentiation by rat bone marrow stromal cells. Calcif. Tissue Int. 64:69-77.
54. Lauffenburger, D. A., and J. J. Linderman. 1993. Receptors: Models for Binding, Trafficking, and Signaling. Oxford University Press, New York.
55. Ornitz, D. M., J. S. Xu, J. S. Colvin, D. G. McEwen, C. A. MacArthur, F. Coulier, G. X. Gao, and M. Goldfarb. 1996. Receptor specificity of the fibroblast growth factor family. J. Biol. Chem. 271:15292-15297.
56. Tanaka, H., H. Ogasa, J. Barnes, and C. T. Liang. 1999. Actions of bFGF on mitogenic activity and lineage expression in rat osteoprogenitor cells: effect of age. Mol. Cell. Endocrinol. 150:1-10.
57. Cowan, C. M., N. Quarto, S. M. Warren, A. Salim, and M. T. Longaker. 2003. Age-related changes in the biomolecular mechanisms of calvarial osteoblast biology affect fibroblast growth factor-2 signaling and osteogenesis. J. Biol. Chem. 278:32005-32013.
58. Kotev-Emeth, S., N. Savion, S. Pri-Chen, and S. Pitaru. 2000. Effect of maturation on the osteogenic response of cultured stromal bone marrow cells to basic fibroblast growth factor. Bone. 27:777-783.
59. Debiais, F., M. Hott, A. M. Graulet, and P. J. Marie. 1998. The effects of fibroblast growth factor-2 on human neonatal calvaria osteoblastic cells are differentiation stage specific. J. Bone Miner. Res. 13:645-654.
60. Roghani, M., and D. Moscatelli. 1992. Basic fibroblast growth-factor is internalized through both receptor-mediated and heparan-sulfate-mediated mechanisms. J. Biol. Chem. 267:22156-22162.
61. Vemuri, S., I. Beylin, V. Sluzky, P. Stratton, G. Eberlein, and Y. J. Wang. 1994. The stability of BFGF against thermal-denaturation. J. Pharm. Pharmacol. 46:481-486.
62. Sommer, A., and D. B. Rifkin. 1989. Interaction of heparin with human basic fibroblast growth-factor - protection of the angiogenic protein from proteolytic degradation by a glycosaminoglycan. J. Cell. Physiol. 138:215-220.
63. Ornitz, D. M., A. Yayon, J. G. Flanagan, C. M. Svahn, E. Levi, and P. Leder. 1992. Heparin is required for cell-free binding of basic fibroblast growth-factor to a soluble receptor and for mitogenesis in whole cells. Mol. Cell. Biol. 12:240-247.
64. Thompson, L. D., M. W. Pantoliano, and B. A. Springer. 1994. Energetic characterization of the basic fibroblast growth-factor heparin interaction: identification of the heparin-binding domain. Biochemistry. 33:3831-3840.
65. Herr, A. B., D. M. Ornitz, R. Sasisekharan, G. Venkataraman, and G. Waksman. 1997. Heparin-induced self-association of fibroblast growth factor-α - evidence for two oligomerization processes. J. Biol. Chem. 272:16382-16389.
66. Gleizes, P. E., J. Noaillacdepeyre, F. Amalric, and N. Gas. 1995. Basic fibroblast growth-factor (Fgf-2) internalization through the heparan-sulfate proteoglycans-mediated pathway - an ultrastructural approach. Eur. J. Cell Biol. 66:47-59.
67. Berrada, S., F. Lefebvre, and M. F. Harmand. 1995. The effect of recombinant human basic fibroblast growth-factor RHFGF-2 on human osteoblast in growth and phenotype expression. In Vitro Cell. Dev. Biol. Anim. 31:698-702.
68. Burgess, W. H., and T. Maciag. 1989. The heparin-binding (fibroblast) growth-factor family of proteins. Annu. Rev. Biochem. 58:575-606.
69. Powell, A. K., D. G. Fernig, and J. E. Turnbull. 2002. Fibroblast growth factor receptors 1 and 2 interact differently with heparin/heparan-sulfate - implications for dynamic assembly of a ternary signaling complex. J. Biol. Chem. 277:28554-28563.
70. Starbuck, C., and D. A. Lauffenburger. 1992. Mathematical model for the effects of epidermal growth factor receptor trafficking dynamics on fibroblast proliferation responses. Biotechnol. Prog. 8:132-143.
71. Moscatelli, D., and P. Devesly. 1990. Turnover of functional basic fibroblast growth factor receptors on the surface of BHK and NIH 3T3 cells. Growth Factors. 3:25-33.
72. Reilly, J. F., E. Mizukoshi, and P. A. Maher. 2004. Ligand dependent and independent internalization and nuclear translocation of fibroblast growth factor (FGF) receptor 1. DNA Cell Biol. 23:538-548.
73. Tkachenko, E., E. Lutgens, R. V. Stan, and M. Simons. 2004. Fibroblast growth factor 2 endocytosis in endothelial cells proceeds via syndecan-4-dependent activation of Rac1 and a Cdc42-dependent macropinocytic pathway. J. Cell Sci. 117:3189-3199.
74. Yanagishita, M., and V. C. Hascall. 1984. Metabolism of proteoglycans in rat ovarian granulosa-cell culture - multiple intracellular degradative pathways and the effect of chloroquine. J. Biol. Chem. 259:270-283.
75. Tang, J. P., J. Julian, S. R. Glasser, and D. D. Carson. 1987. Heparan-sulfate proteoglycan synthesis and metabolism by mouse uterine epithelial cells cultured in vitro. J. Biol. Chem. 262:12832-12842.
76. Sperinde, G. V., and M. A. Nugent. 2000. Mechanisms of fibroblast growth factor 2 intracellular processing: a kinetic analysis of the role of heparan-sulfate proteoglycans. Biochemistry. 39:3788-3796.
77. Tumova, S., B. A. Hatch, D. J. Law, and K. J. Bame. 1999. Basic fibroblast growth factor does not prevent heparan-sulphate proteoglycan catabolism in intact cells, but it alters the distribution of the glycosaminoglycan degradation products. Biochem. J. 337:471-481.
78. Gutfreund, H. 1995. Kinetics for the Life Sciences: Receptors, Transmitters and Catalysts. Cambridge University Press, New York.
79. Nugent, M. A., and E. R. Edelman. 1992. Kinetics of basic fibroblast growth-factor binding to its receptor and heparan-sulfate proteoglycan - a mechanism for cooperativity. Biochemistry. 31:8876-8883.
80. Rusnati, M., C. Urbinati, and M. Presta. 1993. Internalization of basic fibroblast growth-factor (BFGF) in cultured endothelial cells - role of the low affinity heparin-like BFGF receptors. J. Cell. Physiol. 154:152-161.
81. Sperinde, G. V., and M. A. Nugent. 1998. Heparan-sulfate proteoglycans control intracellular processing of bFGF in vascular smooth muscle cells. Biochemistry. 37:13153-13164.
82. Holtrop, M. E. 1990. Light and electron microscopic structure of bone-forming cells. In Bone. B. K. Hall, editor. Telford Press, Cadwell, New Jersey.
83. Lirvall, M., P. Ljungqvist-Hoddelius, A. Wasteson, and K. E. Magnusson. 1996. UVB radiation affects the mobility of epidermal growth factor receptors in human keratinocytes and fibroblasts. Biosci. Rep. 16:227-238.
84. Ljungquist-Hoddelius, P., M. Lirvall, A. Wasteson, and K. E. Magnusson. 1991. Lateral diffusion of PDGF β-receptors in human fibroblasts. Biosci. Rep. 11:43-52.
85. Ljungquist, P., A. Wasteson, and K. E. Magnusson. 1989. Lateral diffusion of plasma-membrane receptors labeled with either platelet-derived growth-factor (PDGF) or wheat-germ agglutinin (WGA) in human polymorphonuclear leukocytes and fibroblasts. Biosci. Rep. 9:63-73.
86. Saxton, M. J., and K. Jacobson. 1997. Single-particle tracking: applications to membrane dynamics. Annu. Rev. Biophys. Biomol. Struct. 26:373-399.
87. Saxton, M. J. 1994. Anomalous diffusion due to obstacles: a Monte Carlo study. Biophys. J. 66:394-401.
88. Saxton, M. J. 1996. Anomalous diffusion due to binding: a Monte Carlo study. Biophys. J. 70:1250-1262.
89. Gospodarowicz, D., and J. S. Moran. 1976. Growth-factors in mammalian-cell culture. Annu. Rev. Biochem. 45:531-558.
90. Malamitsi-Puchner, A., J. Tziotis, A. Tsonou, E. Protonotariou, A. Sarandakou, and G. Creatsas. 2000. Basic fibroblast growth factor: serum levels in the female. Growth Factors. 17:215-220.
91. Moehren, G., N. Markevich, O. Demin, A. Kiyatkin, I. Goryanin, J. B. Hoek, and B. N. Kholodenko. 2002. Temperature dependence of the epidermal growth factor receptor signaling network can be accounted for by a kinetic model. Biochemistry. 41:306-320.
92. Chang, Z., K. Meyer, A. C. Rapraeger, and A. Friedl. 2000. Differential ability of heparan-sulfate proteoglycans to assemble the fibroblast growth factor receptor complex in situ. FASEB J. 14:137-144.
93. Guimond, S., K. Turner, M. Kita, M. Ford-Perriss, and J. Turnbull. 2001. Dynamic biosynthesis of heparan sulphate sequences in developing mouse brain: a potential regulatory mechanism during development. Biochem. Soc. Trans. 29:177-181.
94. Knox, S., C. Merry, S. Stringer, J. Melrose, and J. Whitelock. 2002. Not all perlecans are created equal - interactions with fibroblast growth factor (FGF) 2 and FGF receptors. J. Biol. Chem. 277:14657-14665.
95. Schmidt, A., A. Skaletzrorowski, and E. Buddecke. 1995. Basic fibroblast growth-factor controls the expression and molecular structure of heparan-sulfate in corneal endothelial cells. Eur. J. Biochem. 234:479-484.
96. Schmidt, A., A. Skaletzrorowski, G. Breithardt, and E. Buddecke. 1995. Growth status-dependent changes of BFGF compartmentalization and heparan-sulfate structure in arterial smooth-muscle cells. Eur. J. Cell Biol. 67:130-135.
97. Richardson, T. P., V. Trinkaus-Randall, and M. A. Nugent. 1999. Regulation of basic fibroblast growth factor binding and activity by cell density and heparan-sulfate. J. Biol. Chem. 274:13534-13540.
98. Beresford, J. N., N. S. Fedarko, L. W. Fisher, R. J. Midura, M. Yanagishita, J. D. Termine, and P. G. Robey. 1987. Analysis of the proteoglycans synthesized by human-bone cells in vitro. J. Biol. Chem. 262:17164-17172.
99. Guimond, S. E., and J. E. Turnbull. 1999. Fibroblast growth factor receptor signalling is dictated by specific heparan sulphate saccharides. Curr. Biol. 9:1343-1346.
100. Zandstra, P. W., D. A. Lauffenburger, and C. J. Eaves. 2000. A ligand-receptor signaling threshold model of stem cell differentiation control: a biologically conserved mechanism applicable to hematopoiesis. Blood. 96:1215-1222.
101. Colin, S., J. C. Jeanny, F. Mascarelli, R. Vienet, S. Al-Mahmood, Y. Courtois, and J. Labarre. 1999. In vivo involvement of heparan-sulfate proteoglycan in the bioavailability, internalization, and catabolism of exogenous basic fibroblast growth factor. Mol. Pharmacol. 55:74-82.
102. Williams, K. J., and I. V. Fuki. 1997. Cell-surface heparan-sulfate proteoglycans: dynamic molecules mediating ligand catabolism. Curr. Opin. Lipidol. 8:253-262.
103. Colin, S., F. Mascarelli, J. C. Jeanny, R. Vienet, G. Bouche, Y. Courtois, and J. Labarre. 1997. Comparative study in vivo and in vitro of uniformly C-14-labeled and I-125-labeled recombinant fibroblast growth factor 2. Eur. J. Biochem. 249:473-480.
104. Kwan, C. P., G. Venkataraman, Z. Shriver, R. Raman, D. F. Liu, Y. W. Qi, L. Varticovski, and R. Sasisekharan. 2001. Probing fibroblast growth factor dimerization and role of heparin-like glycosaminoglycans in modulating dimerization and signaling. J. Biol. Chem. 276:23421-23429.
105. Van den Berghe, L., I. Mortier, C. Zanibellato, F. Amalric, H. Prats, and B. Bugler. 1998. FGF-2 dimerization involvement in growth factor mediated cell proliferation but not cell differentiation. Biochem. Biophys. Res. Commun. 252:420-427.
106. Springer, B. A., M. W. Pantoliano, F. A. Barbera, P. L. Gunyuzlu, L. D. Thompson, W. F. Herblin, S. A. Rosenfeld, and G. W. Book. 1994. Identification and concerted function of two receptor-binding surfaces on basic fibroblast growth-factor required for mitogenesis. J. Biol. Chem. 269:26879-26884.
107. 1-phase by a common mechanism. Mol. Biol. Cell. 15:801-814.