PROSITE documentation PDOC00213

{PDOC00213}
{PS00240; RECEPTOR_TYR_KIN_III}
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* Receptor tyrosine kinase class III signature *
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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

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