Interactions of p59fyn and ZAP-70 with T-cell receptor activation motifs: defining the nature of a signalling motif.

• DOI: 10.1128/mcb.14.6.3729
• Publication Date: 2015-10-06T00:40:01Z
• Authors: L K Gauen; Y Zhu; F Letourneur; Q Hu; J B Bolen; L A Matis; R D Klausner; A S Shaw
• Keywords: Sequence motif; Polyproline helix

The tyrosine-based activation motif is a 20- to 25-amino-acid sequence contained in the cytoplasmic domains of many hematopoietic receptors which sufficient by itself reconstitute signalling. This characterized two YXXL/I sequences separated approximately 10 residues. molecular basis signalling this unknown. Here we demonstrate that required and for association with tyrosine kinases p59fyn ZAP-70, suggesting these general feature motif. Focusing on single present epsilon, analyzed residues were critical binding ZAP-70. Surprisingly, found no mutation any residue epsilon resulted loss association. In contrast, mutations at five activating abrogated ZAP-70 binding. Both tyrosines leucine or isoleucine follow them critical. spacing between was also important, as deletion disrupted although not disrupted. Most defined features are therefore requirements Interestingly, interaction dependent presence both SH2 motif, interacts phosphotyrosine cooperative. addition, direct requires prior phosphorylation We propose cells occurs four discrete steps: p59fyn, kinase activity.