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The adapter protein APS associates with the multifunctional docking sites Tyr-568 and Tyr-936 in c-Kit.

Wollberg, Patrik; Lennartsson, Johan; Gottfridsson, Eva; Yoshimura, Akihiko and Rönnstrand, Lars LU (2003) In Biochemical Journal 370(Pt 3). p.1033-1038
Abstract
The adapter protein APS has previously been shown to be involved in recruiting the ubiquitin E3 ligase c-Cbl to the insulin receptor, the platelet-derived growth factor b-receptor and the erythropoietin receptor, leading to increased degradation of the receptors and inhibition of mitogenesis. Here we demonstrate, by use of immobilized synthetic phosphopeptides corresponding to various autophosphorylated tyrosine residues in the receptor for stem-cell factor (c-Kit), that APS preferentially associates with phosphorylated Tyr-568 and Tyr-936. Tyr-568 has previously been identified as the binding site of the Src family of tyrosine kinases, the Csk-homologous kinase CHK, and the protein tyrosine phosphatase SHP-2. We have recently demonstrated... (More)
The adapter protein APS has previously been shown to be involved in recruiting the ubiquitin E3 ligase c-Cbl to the insulin receptor, the platelet-derived growth factor b-receptor and the erythropoietin receptor, leading to increased degradation of the receptors and inhibition of mitogenesis. Here we demonstrate, by use of immobilized synthetic phosphopeptides corresponding to various autophosphorylated tyrosine residues in the receptor for stem-cell factor (c-Kit), that APS preferentially associates with phosphorylated Tyr-568 and Tyr-936. Tyr-568 has previously been identified as the binding site of the Src family of tyrosine kinases, the Csk-homologous kinase CHK, and the protein tyrosine phosphatase SHP-2. We have recently demonstrated that Tyr-936 is an autophosphorylation site involved in binding the adapter proteins Grb2 and Grb7. We could further demonstrate that the critical determinant for binding of APS is the presence of either a leucine or an isoleucine residue in the position +3 to the phosphorylated tyrosine. This allowed us to design mutants that selectively failed to associate with APS, while still associating with Src family members, SHP-2 and Grb2, respectively. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Binding Sites, Tyrosine: metabolism, src Homology Domains, Platelet-Derived Growth Factor: genetics, Receptors, Support, Non-U.S. Gov't, Signal Transduction: physiology, Stem Cell Factor: metabolism, Platelet-Derived Growth Factor: metabolism, Recombinant Fusion Proteins: genetics, Recombinant Fusion Proteins: metabolism, COS Cells, Human, Isoleucine: metabolism, Leucine: metabolism, Mice, Mutagenesis, Site-Directed, Peptides: metabolism, Phosphorylation, Protein Binding, Proteins: metabolism, Proto-Oncogene Protein c-kit: genetics, Proto-Oncogene Protein c-kit: metabolism
in
Biochemical Journal
volume
370
issue
Pt 3
pages
1033 - 1038
publisher
Portland Press Limited
external identifiers
  • wos:000181824800033
  • pmid:12444928
  • scopus:0037444815
ISSN
0264-6021
DOI
10.1042/BJ20020716
language
English
LU publication?
no
id
1159a861-c4f0-494f-88fb-422f6c777fe5 (old id 123146)
date added to LUP
2007-07-27 13:56:17
date last changed
2018-01-07 08:51:31
@article{1159a861-c4f0-494f-88fb-422f6c777fe5,
  abstract     = {The adapter protein APS has previously been shown to be involved in recruiting the ubiquitin E3 ligase c-Cbl to the insulin receptor, the platelet-derived growth factor b-receptor and the erythropoietin receptor, leading to increased degradation of the receptors and inhibition of mitogenesis. Here we demonstrate, by use of immobilized synthetic phosphopeptides corresponding to various autophosphorylated tyrosine residues in the receptor for stem-cell factor (c-Kit), that APS preferentially associates with phosphorylated Tyr-568 and Tyr-936. Tyr-568 has previously been identified as the binding site of the Src family of tyrosine kinases, the Csk-homologous kinase CHK, and the protein tyrosine phosphatase SHP-2. We have recently demonstrated that Tyr-936 is an autophosphorylation site involved in binding the adapter proteins Grb2 and Grb7. We could further demonstrate that the critical determinant for binding of APS is the presence of either a leucine or an isoleucine residue in the position +3 to the phosphorylated tyrosine. This allowed us to design mutants that selectively failed to associate with APS, while still associating with Src family members, SHP-2 and Grb2, respectively.},
  author       = {Wollberg, Patrik and Lennartsson, Johan and Gottfridsson, Eva and Yoshimura, Akihiko and Rönnstrand, Lars},
  issn         = {0264-6021},
  keyword      = {Animals,Binding Sites,Tyrosine: metabolism,src Homology Domains,Platelet-Derived Growth Factor: genetics,Receptors,Support,Non-U.S. Gov't,Signal Transduction: physiology,Stem Cell Factor: metabolism,Platelet-Derived Growth Factor: metabolism,Recombinant Fusion Proteins: genetics,Recombinant Fusion Proteins: metabolism,COS Cells,Human,Isoleucine: metabolism,Leucine: metabolism,Mice,Mutagenesis,Site-Directed,Peptides: metabolism,Phosphorylation,Protein Binding,Proteins: metabolism,Proto-Oncogene Protein c-kit: genetics,Proto-Oncogene Protein c-kit: metabolism},
  language     = {eng},
  number       = {Pt 3},
  pages        = {1033--1038},
  publisher    = {Portland Press Limited},
  series       = {Biochemical Journal},
  title        = {The adapter protein APS associates with the multifunctional docking sites Tyr-568 and Tyr-936 in c-Kit.},
  url          = {http://dx.doi.org/10.1042/BJ20020716},
  volume       = {370},
  year         = {2003},
}