{PDOC00213} {PS00240; RECEPTOR_TYR_KIN_III} {BEGIN} ************************************************ * 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: alpha and beta [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. -Consensus pattern: G-x-H-x-N-[LIVM]-V-N-L-L-G-A-C-T -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: December 2001 / Text revised. [ 1] Yarden Y., Ullrich A. "Growth factor receptor tyrosine kinases." Annu. Rev. Biochem. 57:443-478(1988). PubMed=3052279; DOI=10.1146/annurev.bi.57.070188.002303 [ 2] Hunkapiller T., Hood L. "Diversity of the immunoglobulin gene superfamily." Adv. Immunol. 44:1-63(1989). PubMed=2646860 [ 3] Lee K.-H., Bowen-Pope D.F., Reed R.R. "Isolation and characterization of the alpha platelet-derived growth factor receptor from rat olfactory epithelium." Mol. Cell. Biol. 10:2237-2246(1990). PubMed=2157969 [ 4] Terman B.I., Dougher-Vermazen M., Carrion M.E., Dimitrov D., Armellino D.C., Gospodarowicz D., Bohlen P. "Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor." Biochem. Biophys. Res. Commun. 187:1579-1586(1992). PubMed=1417831 [ 5] 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. "Molecular cloning of a ligand for the flt3/flk-2 tyrosine kinase receptor: a proliferative factor for primitive hematopoietic cells." Cell 75:1157-1167(1993). PubMed=7505204 [ 6] Galland F., Karamysheva A., Pebusque M.J., Borg J.P., Rottapel R., Dubreuil P., Rosnet O., Birnbaum D. "The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor." Oncogene 8:1233-1240(1993). PubMed=8386825 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}