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- * Receptor tyrosine kinase class II 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 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:
-
- - The insulin receptor [2,3].
- - The insulin growth factor I receptor from Human [4], and Drosophila [5].
- - The insulin receptor-related receptor (IRR) [6], which is most probably a
- receptor for a peptide belonging to the insulin family.
- - The putative c-ros receptor [7].
- - The Drosophila developmental protein sevenless [8], a putative receptor for
- positional information required for the formation of the R7 photoreceptor
- cells.
- - The trk family of receptors [9,10], which are high affinity receptors for
- nerve growth factor and related neurotrophic factors (BDNF and NT-3).
- - The putative ltk receptor [11].
-
- 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: D-[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: December 1992 / Text revised.
-
- [ 1] Yarden Y., Ullrich A.
- Annu. Rev. Biochem. 57:443-478(1988).
- [ 2] Ebina Y., Ellis L., Jarnagin K., Edery M., Graf L., Clauser E.,
- Ou J.-H., Masiarz F., Kan Y.W., Goldfine I.D., Roth R.A., Rutter W.J.
- Cell 40:747-758(1985).
- [ 3] Ullrich A., Bell J.R., Chen E.Y., Herrera R., Petruzzelli L.M.,
- Dull T.J., Gray A., Coussens L., Liao Y.-C., Tsubokawa M., Mason A.,
- Seeburg P.H., Grunfeld C., Rosen O.M., Ramachandran J.
- Nature 313:756-761(1985).
- [ 4] Ullrich A., Gray A., Tam A.W., Yang-Feng T., Tsubokawa M., Collins C.,
- Henzel W., Bon T.L., Kathuria S., Chen E., Jacobs S., Francke U.,
- Ramachandran J., Fujita-Yamaguchi Y.
- EMBO J. 5:2503-2512(1986).
- [ 5] Nishida Y., Hata M., Nishizuka Y., Rutter W.J., Ebina Y.
- Biochem. Biophys. Res. Commun. 141:474-481(1986).
- [ 6] Shier P., Watt V.M.
- J. Biol. Chem. 264:14605-14608(1989).
- [ 7] Matsushime H., Wang L.-H., Shibuya M.
- Mol. Cell. Biol. 6:3000-3004(1986).
- [ 8] Hafen E., Basler K., Edstroem J.-E., Rubin G.M.
- Science 236:55-63(1987).
- [ 9] Park M.
- Curr. Biol. 1:248-250(1991).
- [10] Ragsdale C., Woodgett J.
- Nature 350:660-661(1991).
- [11] Krolewski J.J., Dalla-Favera R.
- EMBO J. 10:2911-2919(1991).
-