1000 Titel
  • Analysis of Phosphorylation-dependent Protein Interactions of Adhesion and Degranulation Promoting Adaptor Protein (ADAP) Reveals Novel Interaction Partners Required for Chemokine-directed T cell Migration
1000 Autor/in
  1. Kuropka, Benno |
  2. Witte, Amelie |
  3. Sticht, Jana |
  4. Waldt, Natalie |
  5. Majkut, Paul |
  6. Schraven, Burkhart |
  7. Krause, Eberhard |
  8. Kliche, Stefanie |
  9. Freund, Christian |
  10. Hackenberger, Christian |
1000 Erscheinungsjahr 2015
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2015-11-01
1000 Erschienen in
1000 Quellenangabe
  • 14: 2961-2972
1000 FRL-Sammlung
1000 Verlagsversion
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638039/ |
  • http://doi.org/10.1074/mcp.M115.048249 |
1000 Ergänzendes Material
  • http://www.mcponline.org/content/14/11/2961/suppl/DC1 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Stimulation of T cells leads to distinct changes of their adhesive and migratory properties. Signal propagation from activated receptors to integrins depends on scaffolding proteins such as the adhesion and degranulation promoting adaptor protein (ADAP)1. Here we have comprehensively investigated the phosphotyrosine interactome of ADAP in T cells and define known and novel interaction partners of functional relevance. While most phosphosites reside in unstructured regions of the protein, thereby defining classical SH2 domain interaction sites for master regulators of T cell signaling such as SLP76, Fyn-kinase, and NCK, other binding events depend on structural context. Interaction proteomics using different ADAP constructs comprising most of the known phosphotyrosine motifs as well as the structured domains confirm that a distinct set of proteins is attracted by pY571 of ADAP, including the ζ-chain-associated protein kinase of 70 kDa (ZAP70). The interaction of ADAP and ZAP70 is inducible upon stimulation either of the T cell receptor (TCR) or by chemokine. NMR spectroscopy reveals that the N-terminal SH2 domains within a ZAP70-tandem-SH2 construct is the major site of interaction with phosphorylated ADAP-hSH3N and microscale thermophoresis (MST) indicates an intermediate binding affinity (Kd = 2.3 μM). Interestingly, although T cell receptor dependent events such as T cell/antigen presenting cell (APC) conjugate formation and adhesion are not affected by mutation of Y571, migration of T cells along a chemokine gradient is compromised. Thus, although most phospho-sites in ADAP are linked to T cell receptor related functions we have identified a unique phosphotyrosine that is solely required for chemokine induced T cell behavior.
1000 Fachgruppe
  1. Biologie |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/S3Vyb3BrYSwgQmVubm8=|https://frl.publisso.de/adhoc/creator/V2l0dGUsIEFtZWxpZQ==|https://frl.publisso.de/adhoc/creator/U3RpY2h0LCBKYW5h|https://frl.publisso.de/adhoc/creator/V2FsZHQsIE5hdGFsaWU=|https://frl.publisso.de/adhoc/creator/TWFqa3V0LCBQYXVs|https://frl.publisso.de/adhoc/creator/U2NocmF2ZW4sIEJ1cmtoYXJ0|https://frl.publisso.de/adhoc/creator/S3JhdXNlLCBFYmVyaGFyZA==|https://frl.publisso.de/adhoc/creator/S2xpY2hlLCBTdGVmYW5pZQ==|https://frl.publisso.de/adhoc/creator/RnJldW5kLCBDaHJpc3RpYW4=|http://orcid.org/0000-0001-7457-4742
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1000 Objektart article
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1000 @id frl:6402318.rdf
1000 Erstellt am 2017-05-08T11:36:51.733+0200
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1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Fri Jan 31 01:39:32 CET 2020
1000 Objekt bearb. Mon Apr 30 13:58:19 CEST 2018
1000 Vgl. frl:6402318
1000 Oai Id
  1. oai:frl.publisso.de:frl:6402318 |
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