A scanning peptide array approach uncovers association sites within the JNK/βarrestin signalling complex

Xiang Li, Ruth MacLeod, Allan J. Dunlop, Helen V. Edwards, Noopur Advant, L. C D Gibson, Nicola M. Devine, Kim M. Brown, David R. Adams, Miles D. Houslay, George S. Baillie

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

ßarrestins are molecular scaffolds that can bring together three-component mitogen-activated protein kinase signalling modules to promote signal compartmentalisation. We use peptide array technology to define novel interfaces between components within the c-Jun N-terminal kinase (JNK)/ßarrestin signalling complex. We show that ßarrestin 1 and ßarrestin 2 associate with JNK3 via the kinase N-terminal domain in a region that, surprisingly, does not harbour a known 'common docking' motif. In the N-domain and C-terminus of ßarrestin 1 and ßarrestin 2 we identify two novel apoptosis signal-regulating kinase 1 binding sites and in the N-domain of the ßarrestin 1 and ßarrestin 2 we identify a novel MKK4 docking site. Structured summary: MINT-7263196, MINT-7263175: Arrestin beta-2 (uniprotkb:P32121) binds (MI:0407) to ASK1 (uniprotkb:Q99683) by peptide array (MI:0081). MINT-7263136: JNK3 (uniprotkb:P53779) binds (MI:0407) to Arrestin beta-1 (uniprotkb:P49407) by peptide array (MI:0081). MINT-7263161: JNK3 (uniprotkb:P53779) binds (MI:0407) to Arrestin beta-2 (uniprotkb:P32121) by peptide array (MI:0081). MINT-7263304: Arrestin beta-1 (uniprotkb:P49407) physically interacts (MI:0915) with ASK1 (uniprotkb:Q99683) by anti tag coimmunoprecipitation (MI:0007). MINT-7263286: Arrestin beta-2 (uniprotkb:P32121) binds (MI:0407) to MKK4 (uniprotkb:P45985) by peptide array (MI:0081). MINT-7263231, MINT-7263254: Arrestin beta-1 (uniprotkb:P49407) binds (MI:0407) to ASK1 (uniprotkb:Q99683) by peptide array (MI:0081). MINT-7263269: Arrestin beta-1 (uniprotkb:P49407) binds (MI:0407) to MKK4 (uniprotkb:P45985) by peptide array (MI:0081). © 2009 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)3310-3316
Number of pages7
JournalFEBS Letters
Volume583
Issue number20
DOIs
Publication statusPublished - 20 Oct 2009

Keywords

  • Arrestin
  • ASK1
  • JNK
  • MKK4
  • Peptide array
  • Scaffold

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