A region from the medium chain adaptor subunit (mu) recognizes leucine- and tyrosine-based sorting signals.
Tyrosine-based sorting signals in the cytosolic tails of membrane proteins have been found to bind directly to the medium chain subunit (mu) of the adaptor complexes AP-1 and AP-2. For the leucine-based signals, an interaction with AP-1 and AP-2 has been reported, but no specific interacting subunit has been demonstrated. After searching for molecules interacting with the leucine-based sorting signals within the cytosolic tail of the major histocompatibility complex class II-associated invariant chain using a phage display approach, we identified phage clones with homology to a conserved region of the AP-1 and AP-2 mu chains. To investigate the relevance of these findings, we have expressed regions of mouse mu1 and mu2 chains on phage gene product III and investigated the binding to tail sequences from various transmembrane proteins with known endosomal targeting signals. Enzyme-linked immunosorbent binding assays showed that these phages specifically recognized peptides containing functional leucine- and tyrosine-based sorting signals, suggesting that these regions of the mu1 and mu2 chains interact with both types of sorting signals.
Bremnes
T
T
Department of Molecular Cell Biology, Division of Biology, University of Oslo, 0316 Oslo, Norway.
Lauvrak
V
V
Lindqvist
B
B
Bakke
O
O
D000595:Amino Acid Sequence; D000818:Animals; D010583:Bacteriophage mu; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D007700:Kinetics; D008239:Lysine; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000737:chemistry* / Q000378:metabolism*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014443:Tyrosine
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D014443:Tyrosine; D008239:Lysine