CKAP4/p63 is a Receptor for the Frizzled-8 Protein-Related Antiproliferative Factor from Interstitial Cystitis Patients
The Journal of Biological Chemistry
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.
Amino acid sequence, antibodies, monoclonal, base sequence, cells, cultured, cystitis, interstitial, epithelial cells, glycoproteins, protein binding, RNA, urinary bladder
Conrads, Thomas P.; Tocci, Gillian M.; Hood, Brian L.; Zhang, Chen-Ou; Guo, Li; Koch, Kristopher R.; Michejda, Christopher J.; Veenstra, Timothy D.; and Keay, Susan K., "CKAP4/p63 is a Receptor for the Frizzled-8 Protein-Related Antiproliferative Factor from Interstitial Cystitis Patients" (2006). Pharmaceutical Sciences Faculty Publications. 398.