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Conrads, T.P. et al.

CKAP4/ p63 Is a Receptor for the Frizzled-8 Protein-related Antiproliferative Factor from Interstitial Cystitis Patients.

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.[1]

References

CKAP4/p63 Is a Receptor for the Frizzled-8 Protein-related Antiproliferative Factor from Interstitial Cystitis Patients. Conrads, T.P., Tocci, G.M., Hood, B.L., Zhang, C.O., Guo, L., Koch, K.R., Michejda, C.J., Veenstra, T.D., Keay, S.K. J. Biol. Chem. (2006) [Pubmed]

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