Antiproliferative Factor-Induced Changes in Phosphorylation and Palmitoylation of Cytoskeleton-Associated Protein-4 Regulate Its Nuclear Translocation and DNA Binding
Cytoskeleton-associated protein 4 (CKAP4) is a reversibly palmitoylated and phosphorylated transmembrane protein that functions as a high-affinity receptor for antiproliferative factor (APF)—a sialoglycopeptide secreted from bladder epithelial cells of patients with interstitial cystitis (IC). Palmi...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2012/150918 |
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| author | David A. Zacharias Matthew Mullen Sonia Lobo Planey |
| author_facet | David A. Zacharias Matthew Mullen Sonia Lobo Planey |
| author_sort | David A. Zacharias |
| collection | DOAJ |
| description | Cytoskeleton-associated protein 4 (CKAP4) is a reversibly palmitoylated and phosphorylated transmembrane protein that functions as a high-affinity receptor for antiproliferative factor (APF)—a sialoglycopeptide secreted from bladder epithelial cells of patients with interstitial cystitis (IC). Palmitoylation of CKAP4 by the palmitoyl acyltransferase, DHHC2, is required for its cell surface localization and subsequent APF signal transduction; however, the mechanism for APF signal transduction by CKAP4 is unknown. In this paper, we demonstrate that APF treatment induces serine phosphorylation of residues S3, S17, and S19 of CKAP4 and nuclear translocation of CKAP4. Additionally, we demonstrate that CKAP4 binds gDNA in a phosphorylation-dependent manner in response to APF treatment, and that a phosphomimicking, constitutively nonpalmitoylated form of CKAP4 localizes to the nucleus, binds DNA, and mimics the inhibitory effects of APF on cellular proliferation. These results reveal a novel role for CKAP4 as a downstream effecter for APF signal transduction. |
| format | Article |
| id | doaj-art-ffaa679583f84271a2ad6517b2ab23b2 |
| institution | Kabale University |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj-art-ffaa679583f84271a2ad6517b2ab23b22025-08-20T03:25:56ZengWileyInternational Journal of Cell Biology1687-88761687-88842012-01-01201210.1155/2012/150918150918Antiproliferative Factor-Induced Changes in Phosphorylation and Palmitoylation of Cytoskeleton-Associated Protein-4 Regulate Its Nuclear Translocation and DNA BindingDavid A. Zacharias0Matthew Mullen1Sonia Lobo Planey2Whitney Laboratory, Department of Neuroscience, University of Florida, St. Augustine, FL 32080, USADepartment of Basic Sciences, The Commonwealth Medical College, Scranton, PA 18509, USADepartment of Basic Sciences, The Commonwealth Medical College, Scranton, PA 18509, USACytoskeleton-associated protein 4 (CKAP4) is a reversibly palmitoylated and phosphorylated transmembrane protein that functions as a high-affinity receptor for antiproliferative factor (APF)—a sialoglycopeptide secreted from bladder epithelial cells of patients with interstitial cystitis (IC). Palmitoylation of CKAP4 by the palmitoyl acyltransferase, DHHC2, is required for its cell surface localization and subsequent APF signal transduction; however, the mechanism for APF signal transduction by CKAP4 is unknown. In this paper, we demonstrate that APF treatment induces serine phosphorylation of residues S3, S17, and S19 of CKAP4 and nuclear translocation of CKAP4. Additionally, we demonstrate that CKAP4 binds gDNA in a phosphorylation-dependent manner in response to APF treatment, and that a phosphomimicking, constitutively nonpalmitoylated form of CKAP4 localizes to the nucleus, binds DNA, and mimics the inhibitory effects of APF on cellular proliferation. These results reveal a novel role for CKAP4 as a downstream effecter for APF signal transduction.http://dx.doi.org/10.1155/2012/150918 |
| spellingShingle | David A. Zacharias Matthew Mullen Sonia Lobo Planey Antiproliferative Factor-Induced Changes in Phosphorylation and Palmitoylation of Cytoskeleton-Associated Protein-4 Regulate Its Nuclear Translocation and DNA Binding International Journal of Cell Biology |
| title | Antiproliferative Factor-Induced Changes in Phosphorylation and Palmitoylation of Cytoskeleton-Associated Protein-4 Regulate Its Nuclear Translocation and DNA Binding |
| title_full | Antiproliferative Factor-Induced Changes in Phosphorylation and Palmitoylation of Cytoskeleton-Associated Protein-4 Regulate Its Nuclear Translocation and DNA Binding |
| title_fullStr | Antiproliferative Factor-Induced Changes in Phosphorylation and Palmitoylation of Cytoskeleton-Associated Protein-4 Regulate Its Nuclear Translocation and DNA Binding |
| title_full_unstemmed | Antiproliferative Factor-Induced Changes in Phosphorylation and Palmitoylation of Cytoskeleton-Associated Protein-4 Regulate Its Nuclear Translocation and DNA Binding |
| title_short | Antiproliferative Factor-Induced Changes in Phosphorylation and Palmitoylation of Cytoskeleton-Associated Protein-4 Regulate Its Nuclear Translocation and DNA Binding |
| title_sort | antiproliferative factor induced changes in phosphorylation and palmitoylation of cytoskeleton associated protein 4 regulate its nuclear translocation and dna binding |
| url | http://dx.doi.org/10.1155/2012/150918 |
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