Identification and Characterization of Internalization Signal of the Prostate Specific Membrane Antigen
Abstract
Prostate specific membrane antigen is expressed in large amounts in prostate cancer cells and in metastatic deposits. We have identified monoclonal antibodies that are specifically internalized by prostate cancer cells. Characterization of internalization mechanisms by prostate cancer cells is crucial for the improvement of immunotherapeutic approaches for prostate cancer. Internalization and movement of proteins through endosomes and lysosomes are mediated by internalization signals present in the cytoplasmic tail of internalized proteins. Using plasmid constructs that contain various deletions and point mutations in the cytoplasmic tail of PSMA we have characterized a di-leucine motif in the cytoplasmic tail of PSMA as an internalization signal that mediates the internalization of monoclonal antibodies raised against PSMA. We also found that the di-leucine motif of PSMA is sufficient to target PSMA to lysosomes. These findings should provide insights into strategies to improve the efficacy of anti-PSMA antibodies for immunotherapy for prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2001
- Accession Number
- ADB266571
Entities
People
- Ayyappan Rajasekaran
Organizations
- University of California, Los Angeles