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An Essential Heparin-Binding Domain in the Fibroblast Growth Factor Receptor Kinase
Abstract
Heparin or heparin-like heparan sulfate proteoglycans are obligatory for activity of the heparin-binding fibroblast growth factor (FGF) family. Heparin interacts independently of FGF ligand with a specific sequence (K18K) in one of the immunoglobulin-like loops in the extracellular domain of the FGF receptor tyrosine kinase transmembrane glycoprotein. A synthetic peptide corresponding to K18K inhibited heparin and heparin-dependent FGF binding to the receptor. K18K and an antibody to K18K were antagonists of FGF-stimulated cell growth. Point mutations of lysine residues in the K18K sequence abrogated both heparin- and ligand-binding activities of the receptor kinase. The results indicate that the FGF receptor is a ternary complex of heparan sulfate proteoglycan, tyrosine kinase transmembrane glycoprotein, and ligand.
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Cites
Yayon, A., Klagsbrun, M., Esko, J. D., Leder, P., & Ornitz, D. M. (1991) · Cell · doi:10.1016/0092-8674(91)90512-w · Cited by 2,440
Cited by
Fibroblast growth factors, their receptors and signaling
Powers, C. J., McLeskey, S. W., & Wellstein, A. (2000) · Endocrine-related cancer · doi:10.1677/erc.0.0070165 · Cited by 1,332
Spivak-Kroizman, T., Lemmon, M. A., Dikic, I., Ladbury, J. E., Pinchasi, D., Huang, J., Jaye, M., Crumley, G., Schlessinger, J., & Lax, I. (1994) · Cell · doi:10.1016/0092-8674(94)90032-9 · Cited by 658
Nugent, M. A., & Iozzo, R. V. (2000) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(99)00123-5 · Cited by 547
Microbial adherence to and invasion through proteoglycans
Rostand, K. S., & Esko, J. D. (1997) · Infection and Immunity · doi:10.1128/iai.65.1.1-8.1997 · Cited by 490
Guimond, S., Maccarana, M., Olwin, B. B., Lindahl, U., & Rapraeger, A. C. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)80471-2 · Cited by 481
Metadata
- Authors
- Kan, M., Wang, F., Xu, J., Crabb, J. W., Hou, J., & McKeehan, W. L.
- Venue
- Science
- Published
- 1993-03-26
- Volume
- 259
- Issue
- 5103
- Pages
- 1918-1921
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2050256171
- Cited by
- 516
- References
- 1
- FWCI
- 18.36
- Type
- journal article
- Language
- en
- Open access
- closed
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- Kan, M., Wang, F., Xu, J., Crabb, J. W., Hou, J., & McKeehan, W. L. (1993). An Essential Heparin-Binding Domain in the Fibroblast Growth Factor Receptor Kinase. Science. https://doi.org/10.1126/science.8456318
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
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.
