PROSITE documentation PDOC00213
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.


Technical section

PROSITE method (with tools and information) covered by this documentation:

RECEPTOR_TYR_KIN_III, PS00240; Receptor tyrosine kinase class III signature  (PATTERN)


1AuthorsYarden Y. Ullrich A.
TitleGrowth factor receptor tyrosine kinases.
SourceAnnu. Rev. Biochem. 57:443-478(1988).
PubMed ID3052279

2AuthorsHunkapiller T. Hood L.
TitleDiversity of the immunoglobulin gene superfamily.
SourceAdv. Immunol. 44:1-63(1989).
PubMed ID2646860

3AuthorsLee K.-H. Bowen-Pope D.F. Reed R.R.
TitleIsolation and characterization of the alpha platelet-derived growth factor receptor from rat olfactory epithelium.
SourceMol. Cell. Biol. 10:2237-2246(1990).
PubMed ID2157969

4AuthorsTerman B.I. Dougher-Vermazen M. Carrion M.E. Dimitrov D. Armellino D.C. Gospodarowicz D. Bohlen P.
TitleIdentification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor.
SourceBiochem. Biophys. Res. Commun. 187:1579-1586(1992).
PubMed ID1417831

5AuthorsLyman 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.
TitleMolecular cloning of a ligand for the flt3/flk-2 tyrosine kinase receptor: a proliferative factor for primitive hematopoietic cells.
SourceCell 75:1157-1167(1993).
PubMed ID7505204

6AuthorsGalland F. Karamysheva A. Pebusque M.J. Borg J.P. Rottapel R. Dubreuil P. Rosnet O. Birnbaum D.
TitleThe FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor.
SourceOncogene 8:1233-1240(1993).
PubMed ID8386825

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