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

Patrik Wollberg, Johan Lennartsson, Eva Gottfridsson, Akihiko Yoshimura, Lars Rönnstrand

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 β-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.

Original languageEnglish
Pages (from-to)1033-1038
Number of pages6
JournalBiochemical Journal
Volume370
Issue number3
DOIs
Publication statusPublished - 2003 Mar 15
Externally publishedYes

Fingerprint

Tyrosine
Non-Receptor Type 11 Protein Tyrosine Phosphatase
Proto-Oncogene Proteins c-kit
Erythropoietin Receptors
Platelet-Derived Growth Factor Receptors
Phosphopeptides
Ubiquitin-Protein Ligases
src-Family Kinases
Isoleucine
Insulin Receptor
Leucine
Carrier Proteins
Proteins
Phosphotransferases
Binding Sites
Degradation
Inhibition (Psychology)

Keywords

  • APS
  • c-Cbl
  • c-Kit
  • Ubiquitination
  • v-Kit

ASJC Scopus subject areas

  • Biochemistry

Cite this

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; Rönnstrand, Lars.

In: Biochemical Journal, Vol. 370, No. 3, 15.03.2003, p. 1033-1038.

Research output: Contribution to journalArticle

Wollberg, Patrik ; Lennartsson, Johan ; Gottfridsson, Eva ; Yoshimura, Akihiko ; Rönnstrand, Lars. / The adapter protein APS associates with the multifunctional docking sites Tyr-568 and Tyr-936 in c-Kit. In: Biochemical Journal. 2003 ; Vol. 370, No. 3. pp. 1033-1038.
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