PROSITE documentation PDOC00212

{PDOC00212}
{PS00239; RECEPTOR_TYR_KIN_II}
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* Receptor tyrosine kinase class II 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 prototype for class II RTK's is the
insulin receptor,  a heterotetramer of two alpha and two beta chains linked by
disulfide bonds.  The  alpha  and  beta  chains  are  cleavage  products  of a
precursor molecule. The alpha chain contains the ligand binding site, the beta
chain transverses  the  membrane  and  contains  the  tyrosine  protein kinase
domain. The receptors currently known to belong to class II are:

 - Insulin receptor from vertebrates.
 - Insulin growth factor I receptor from mammals.
 - Insulin  receptor-related receptor (IRR), which is most probably a receptor
   for a peptide belonging to the insulin family.
 - Insects insulin-like receptors.
 - Molluscan insulin-related peptide(s) receptor (MIP-R).
 - Insulin-like peptide receptor from Branchiostoma lanceolatum.
 - The  Drosophila  developmental  protein  sevenless, a putative receptor for
   positional information required for the formation of  the  R7 photoreceptor
   cells.
 - The  trk  family  of receptors  (NTRK1,  NTRK2  and  NTRK3), which are high
   affinity receptors for nerve growth factor and related neurotrophic factors
   (BDNF and NT-3).

And the following uncharacterized receptors:

 - ROS.
 - LTK (TYK1).
 - EDDR1 (cak, TRKE, RTK6).
 - NTRK3 (Tyro10, TKT).
 - A sponge putative receptor tyrosine kinase.

While only the insulin and the insulin growth factor I  receptors are known to
exist in the tetrameric conformation specific to class II RTK's, all the above
proteins share extensive homologies in their kinase domain,  especially around
the putative  site  of  autophosphorylation.  Hence,  we developed a signature
pattern for  this  class of RTK's, which includes the tyrosine residue, itself
probably autophosphorylated.

-Consensus pattern: [DN]-[LIV]-Y-x(3)-Y-Y-R
                    [The second Y is the autophosphorylation site]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: November 1997 / 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

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