Prostate-specific membrane antigen association with filamin A modulates its internalization and NAALADase activity.
Prostate-specific membrane antigen (PMSA) is an integral membrane protein highly expressed by prostate cancer cells. We reported previously that PSMA undergoes internalization via clathrin-coated pits (Liu et al., Cancer Res., 58: 4055-4060, 1998). In this study we demonstrate that filamin A, an actin cross-linking protein, associates with the cytoplasmic tail of PSMA and that this association of PSMA with filamin is involved in its localization to the recycling endosomal compartment. By ectopically expressing PSMA in filamin-negative and -positive cell lines, we additionally show that filamin binding to PSMA reduces the internalization rate of PSMA and its N-acelylated-alpha linked-acidic dipeptidase activity. These results suggest that filamin might be an important regulator of PSMA function.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
Gopalakrishnapillai
G
Anilkumar
Sigrid A
SA
Rajasekaran
Song
S
Wang
Oliver
O
Hankinson
Neil H
NH
Bander
Ayyappan K
AK
Rajasekaran
D000595:Amino Acid Sequence; D000954:Antigens, Surface; D002268:Carboxypeptidases / Q000378:metabolism*; D003285:Contractile Proteins / Q000378:metabolism*; D064448:Filamins; D043425:Glutamate Carboxypeptidase II; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; D002268:Carboxypeptidases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II