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| PROSITE documentation PDOC00213 [for PROSITE entry PS00240] |
Receptor tyrosine kinase class III signature
A number of growth factors stimulate mitogenesis by interacting with a family of cell surface receptors which possess an intrinsic, ligand-sensitive, protein tyrosine kinase activity [1]. These receptor tyrosine kinases (RTK) all share the same topology: an extracellular ligand-binding domain, a single transmembrane region and a cytoplasmic kinase domain. However they can be classified into at least five groups. The class III RTK's are characterized by the presence of five to seven immunoglobulin-like domains [2] in their extracellular section. Their kinase domain differs from that of other RTK's by the insertion of a stretch of 70 to 100 hydrophilic residues in the middle of this domain. The receptors currently known to belong to class III are:
- Platelet-derived growth factor receptor (PDGF-R). PDGF-R exists as a homo- or heterodimer of two related chains: α and β [3].
- Macrophage colony stimulating factor receptor (CSF-1-R) (also known as the fms oncogene).
- Stem cell factor (mast cell growth factor) receptor (also known as the kit oncogene).
- Vascular endothelial growth factor (VEGF) receptors Flt-1 and Flk-1/KDR [4].
- Fl cytokine receptor Flk-2/Flt-3 [5].
- The putative receptor Flt-4 [6].
We developed a signature pattern for this class of RTK's which is based on a conserved region in the kinase domain.
Last update:December 2001 / Text revised.
PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Yarden Y. Ullrich A. |
| Title | Growth factor receptor tyrosine kinases. | |
| Source | Annu. Rev. Biochem. 57:443-478(1988). | |
| PubMed ID | 3052279 | |
| DOI | 10.1146/annurev.bi.57.070188.002303 |
| 2 | Authors | Hunkapiller T. Hood L. |
| Title | Diversity of the immunoglobulin gene superfamily. | |
| Source | Adv. Immunol. 44:1-63(1989). | |
| PubMed ID | 2646860 |
| 3 | Authors | Lee K.-H. Bowen-Pope D.F. Reed R.R. |
| Title | Isolation and characterization of the alpha platelet-derived growth factor receptor from rat olfactory epithelium. | |
| Source | Mol. Cell. Biol. 10:2237-2246(1990). | |
| PubMed ID | 2157969 |
| 4 | Authors | Terman B.I. Dougher-Vermazen M. Carrion M.E. Dimitrov D. Armellino D.C. Gospodarowicz D. Bohlen P. |
| Title | Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. | |
| Source | Biochem. Biophys. Res. Commun. 187:1579-1586(1992). | |
| PubMed ID | 1417831 |
| 5 | Authors | Lyman S.D. James L. Vanden Bos T. de Vries P. Brasel K. Gliniak B. Hollingsworth L.T. Picha K.S. McKenna H.J. Splett R.R. |
| Title | Molecular cloning of a ligand for the flt3/flk-2 tyrosine kinase receptor: a proliferative factor for primitive hematopoietic cells. | |
| Source | Cell 75:1157-1167(1993). | |
| PubMed ID | 7505204 |
| 6 | Authors | Galland F. Karamysheva A. Pebusque M.J. Borg J.P. Rottapel R. Dubreuil P. Rosnet O. Birnbaum D. |
| Title | The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor. | |
| Source | Oncogene 8:1233-1240(1993). | |
| PubMed ID | 8386825 |
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