CKAP4/p63 Is a Receptor for the Frizzled-8 Protein-related Antiproliferative Factor from Interstitial Cystitis Patients
Copyright policy )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.
- University of Maryland School of Medicine United States
- National Institutes of Health United States
- Veterans Health Administration United States
- University of Maryland, Baltimore United States
- National Institute of Health Pakistan
Base Sequence, Molecular Sequence Data, Urinary Bladder, Cystitis, Interstitial, Antibodies, Monoclonal, Membrane Proteins, Epithelial Cells, Receptors, Cell Surface, Humans, Intercellular Signaling Peptides and Proteins, Amino Acid Sequence, RNA, Small Interfering, Cells, Cultured, Glycoproteins, HeLa Cells, Protein Binding
Base Sequence, Molecular Sequence Data, Urinary Bladder, Cystitis, Interstitial, Antibodies, Monoclonal, Membrane Proteins, Epithelial Cells, Receptors, Cell Surface, Humans, Intercellular Signaling Peptides and Proteins, Amino Acid Sequence, RNA, Small Interfering, Cells, Cultured, Glycoproteins, HeLa Cells, Protein Binding
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