A novel cytoplasmic tail MXXXL motif mediates the internalization of prostate-specific membrane antigen. Academic Article uri icon

Overview

abstract

  • Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed at high levels in prostate cancer and in tumor-associated neovasculature. In this study, we report that PSMA is internalized via a clathrin-dependent endocytic mechanism and that internalization of PSMA is mediated by the five N-terminal amino acids (MWNLL) present in its cytoplasmic tail. Deletion of the cytoplasmic tail abolished PSMA internalization. Mutagenesis of N-terminal amino acid residues at position 2, 3, or 4 to alanine did not affect internalization of PSMA, whereas mutation of amino acid residues 1 or 5 to alanine strongly inhibited internalization. Using a chimeric protein composed of Tac antigen, the alpha-chain of interleukin 2-receptor, fused to the first five amino acids of PSMA (Tac-MWNLL), we found that this sequence is sufficient for PSMA internalization. In addition, inclusion of additional alanines into the MWNLL sequence either in the Tac chimera or the full-length PSMA strongly inhibited internalization. From these results, we suggest that a novel MXXXL motif in the cytoplasmic tail mediates PSMA internalization. We also show that dominant negative micro2 of the adaptor protein (AP)-2 complex strongly inhibits the internalization of PSMA, indicating that AP-2 is involved in the internalization of PSMA mediated by the MXXXL motif.

publication date

  • October 3, 2003

Research

keywords

  • Adaptor Protein Complex 2
  • Antigens, Surface
  • Clathrin
  • Endocytosis
  • Glutamate Carboxypeptidase II

Identity

PubMed Central ID

  • PMC284788

Scopus Document Identifier

  • 0345306595

Digital Object Identifier (DOI)

  • 10.1091/mbc.e02-11-0731

PubMed ID

  • 14528023

Additional Document Info

volume

  • 14

issue

  • 12