Identification and Characterization of Internalization Signal of the Prostate Specific Membrane Antigen

Abstract

The purpose of this award was to identify and characterize an internalization signal in the cytoplasmic tail of prostate specific membrane antigen (PSMA, transmembrane protein abundantly expressed in prostate cancer cells. These studies should aid in understanding the mechanism of antibody uptake and fate of the internalized antibody to improve antibody delivery approaches for immunotherapy for prostate cancer., We have now established and standardized a culture model to study internalization signal of PSMA. In addition we have determined that the cytoplasmic tail of PSMA has an internalization signal. An alanine scan mutagenesis approach in which each of the amino acids in the cytoplasmic tail is mutated to an alanine indicated that a di-leucine like motif in the cytoplasmic tail of PSMA might be involved in its internalization. Further mutagenesis approaches revealed that the N-terminal first five amino acids forms a novel endocytic determinant that render internalization function to a non-internalized protein. Thus we have now conclusively determined the endocytic determinant of PSMA.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2001
Accession Number
ADB283519

Entities

People

  • Ayyappan K. Rajasekaran

Organizations

  • University of California, Los Angeles

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Antibodies
  • Biomedical Research
  • Cell Line
  • Cell Membrane
  • Cells
  • Chemistry
  • Confocal Microscopy
  • Governments
  • Molecules
  • Neoplasms
  • Peptide Growth Factors
  • Prostate
  • Prostate Cancer
  • Proteins
  • Rodents
  • Therapy

Fields of Study

  • Biology

Readers

  • Analytical Chemistry
  • Oncology (Cancer Research).
  • Prostate Cancer Biology.

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech