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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/123146
- author
- Wollberg, Patrik
; Lennartsson, Johan
; Gottfridsson, Eva
; Yoshimura, Akihiko
and Rönnstrand, Lars
LU
- publishing date
- 2003
- 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
- external identifiers
-
- wos:000181824800033
- pmid:12444928
- scopus:0037444815
- ISSN
- 0264-6021
- DOI
- 10.1042/BJ20020716
- language
- English
- LU publication?
- no
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)
- id
- 1159a861-c4f0-494f-88fb-422f6c777fe5 (old id 123146)
- date added to LUP
- 2016-04-01 15:52:42
- date last changed
- 2022-01-28 07:44:10
@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}},
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}},
language = {{eng}},
number = {{Pt 3}},
pages = {{1033--1038}},
publisher = {{Portland Press}},
series = {{Biochemical Journal}},
title = {{The adapter protein APS associates with the multifunctional docking sites Tyr-568 and Tyr-936 in c-Kit.}},
url = {{https://lup.lub.lu.se/search/files/4500598/624009.pdf}},
doi = {{10.1042/BJ20020716}},
volume = {{370}},
year = {{2003}},
}