Inhibition of the interaction between tyrosine-based motifs and the medium chain subunit af the AP-2 adaptor complex by specific tyrphostins

C Crump, Joanna Louise Parish, D Stephens, G Banting

Research output: Contribution to journalArticlepeer-review

Abstract

Several intracellular membrane trafficking events are mediated by tyrosine-containing motifs found within the cytosolic domains of certain integral membrane proteins. Many of these tyrosine motifs conform to the consensus YXX Phi, (where Phi represents a bulky hydrophobic residue). This YXX Phi motif has been shown to interact with the medium chain subunits of adaptor complexes that generally link. relevant integral membrane protein cytosolic domains to the clathrin coat involved in vesicle formation. The motif YXX Phi, is also very similar to motifs that are targets for phosphorylation by tyrosine kinases. Tyrosine kinase inhibitors known as tyrphostins are structural analogues of tyrosine, and so it is possible that tyrphostins could also inhibit interactions between medium chains and YXX Phi, motifs. TGN38 is a type I integral membrane protein containing a tyrosine motif, YQRL, within the cytosolic domain. We have previously shown that this motif interacts directly with the medium chain subunit of the plasma membrane localized AP-2 adaptor complex (mu 2) We have investigated a range of tyrphostins and demonstrated a specific inhibition of the interaction between mu 2 and the TGN38 cytosolic domain by tyrphostin A23 through in vitro analysis and the yeast two-hybrid system. These data raise the exciting possibility that different membrane traffic events could be inhibited by specific tyrphostins.

Original languageEnglish
Pages (from-to)28073-28077
Number of pages5
JournalJournal of Biological Chemistry
Volume273
Issue number43
Publication statusPublished - 23 Oct 1998

Keywords

  • TRANS-GOLGI NETWORK
  • CYTOPLASMIC DOMAIN
  • INTERNALIZATION MOTIF
  • CELL-PROLIFERATION
  • MEMBRANE-PROTEIN
  • SORTING SIGNALS
  • TGN38
  • SEQUENCE
  • KINASE
  • ENDOCYTOSIS

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