Beschreibung:
<jats:p>Thioredoxin‐interacting protein (<jats:styled-content style="fixed-case">TXNIP</jats:styled-content>) is a multifunctional protein involved in diverse cellular processes such as cell proliferation and apoptosis. <jats:styled-content style="fixed-case">TXNIP</jats:styled-content> stability is controlled by the ubiquitin–proteasome pathway, and the E3 ubiquitin ligase Itch directly interacts with <jats:styled-content style="fixed-case">TXNIP</jats:styled-content> via <jats:styled-content style="fixed-case">PP</jats:styled-content>xY motifs of <jats:styled-content style="fixed-case">TXNIP</jats:styled-content>. In a previously published study, we have shown that phosphorylation of the <jats:styled-content style="fixed-case">PP</jats:styled-content>xY tyrosyl residue switches <jats:styled-content style="fixed-case">TXNIP</jats:styled-content> selectivity between different binding partners. Here, we describe that tyrosine‐phosphorylated <jats:styled-content style="fixed-case">PP</jats:styled-content>xY motifs also bind to <jats:styled-content style="fixed-case">SH</jats:styled-content>2 domains of Vav2 and Src with dissociation constants around 10 μ<jats:sc>m</jats:sc> and that phosphorylation is indispensable for these interactions as well. The crystal structure of the complex between a phosphorylated <jats:styled-content style="fixed-case">PP</jats:styled-content>xY motif, and the <jats:styled-content style="fixed-case">SH</jats:styled-content>2 domain of Vav2 reveals a conserved recognition mechanism.</jats:p>