Pharmaceutical Sciences Faculty Publications

CKAP4/p63 is a Receptor for the Frizzled-8 Protein-Related Antiproliferative Factor from Interstitial Cystitis Patients

Document Type

Article

Publication Date

12-8-2006

Journal Title

The Journal of Biological Chemistry

ISSN

0021-9258

Volume

281

Issue

49

First Page

37836

Last Page

37843

DOI

10.1074/jbc.M604581200

PubMed ID

17030514

Abstract

Antiproliferative factor (APF) is a low molecular weight sialoglycopeptide that is secreted by bladder cells from interstitial cystitis patients and is a potent inhibitor of both normal bladder epithelial and bladder carcinoma cell proliferation. We hypothesized that APF may produce its antiproliferative effects by binding to a transmembrane receptor. This study demonstrates that cytoskeleton-associated protein 4/p63 (CKAP4/p63), a type II transmembrane receptor, binds with high affinity to APF. The antiproliferative activity of APF is effectively inhibited by preincubation with anti-CKAP4/p63-specific antibodies, as well as by short interfering RNA knockdown of CKAP4/p63. Immunofluorescent confocal microscopy showed co-localization of anti-CKAP4/p63 and rhodamine-labeled synthetic APF binding in both cell membrane and perinuclear areas. APF also inhibits the proliferation of HeLa cervical carcinoma cells that are known to express CKAP4/p63. These data indicate that CKAP4/p63 is an important epithelial cell receptor for APF.

Keywords

Amino acid sequence, antibodies, monoclonal, base sequence, cells, cultured, cystitis, interstitial, epithelial cells, glycoproteins, protein binding, RNA, urinary bladder

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