Document Detail


A novel cytoplasmic tail MXXXL motif mediates the internalization of prostate-specific membrane antigen.
MedLine Citation:
PMID:  14528023     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Sigrid A Rajasekaran; Gopalakrishnapillai Anilkumar; Eri Oshima; James U Bowie; He Liu; Warren Heston; Neil H Bander; Ayyappan K Rajasekaran
Related Documents :
23099563 - Influence of trace elements on stabilization of aqueous solutions of ascorbic acid.
15901693 - Structural comparison of ten serotypes of staphylocoagulases in staphylococcus aureus.
24386573 - Addition of multimodal therapy to standard management of steady state sickle cell disease.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2003-10-03
Journal Detail:
Title:  Molecular biology of the cell     Volume:  14     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-11-25     Completed Date:  2004-04-07     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4835-45     Citation Subset:  IM    
Affiliation:
Department of Pathology and Laboratory Medicine, Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA. arajasekaran@mednet.ucla.edu
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adaptor Protein Complex 2 / metabolism*
Amino Acid Motifs / physiology
Animals
Antigens, Surface / chemistry,  genetics,  metabolism*
COS Cells
Cercopithecus aethiops
Clathrin / metabolism*
Endocytosis / physiology*
Glutamate Carboxypeptidase II / chemistry,  genetics,  metabolism*
HeLa Cells
Humans
Microscopy, Confocal
Microscopy, Fluorescence
Models, Molecular
Mutation
Plasmids / genetics
Protein Binding
Receptors, Interleukin-2 / metabolism
Grant Support
ID/Acronym/Agency:
T32CA09056/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Protein Complex 2; 0/Antigens, Surface; 0/Clathrin; 0/Receptors, Interleukin-2; EC 3.4.17.21/Glutamate Carboxypeptidase II; EC 3.4.17.21/glutamate carboxypeptidase II, human
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Targeting of a tropomyosin isoform to short microfilaments associated with the Golgi complex.
Next Document:  Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regul...