Tyrosine-phosphorylation of the scaffold protein ADAP and its role in T cell signaling

ABSTRACT

Introduction: The Adhesion and Degranulation promoting Adaptor Protein (ADAP) is phosphorylated upon T cell activation and acts as a scaffold for the formation of a signaling complex that integrates molecular interactions between T cell or chemokine receptors, the actin cytoskeleton, and integrin-mediated cellular adhesion and migration.

Areas covered: This article reviews current knowledge of the functions of the adapter protein ADAP in T cell signaling with a focus on the role of individual phosphotyrosine (pY) motifs for SH2 domain mediated interactions. The data presented was obtained from literature searches (PubMed) as well as the authors own research on the topic.

Expert commentary: ADAP can be regarded as a paradigmatic example of how tyrosine phosphorylation sites serve as dynamic interaction hubs. Molecular crowding at unstructured and redundant sites (pY595, pY651) is contrasted by more specific interactions enabled by the three-dimensional environment of a particular phosphotyrosine motif (pY571).

KEYWORDS:

• Affinity purification–mass spectrometry
• quantitative proteomics
• T cell signaling
• tyrosine phosphorylation
• scaffold protein
• pulldown experiment

Declaration of interest

This work was supported by the DFG grants SFB 854 (B19, B12 and B10), SFB958 (Z3) and SFB765 (C4). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.