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Antiproliferative factor-induced changes in phosphorylation and palmitoylation of cytoskeleton-associated protein-4

David A Zacharias1, Matthew Mullen, Sonia Lobo Planey

  • 1Whitney Laboratory, Department of Neuroscience, University of Florida, St. Augustine, FL 32080, USA.

International Journal of Cell Biology
|April 27, 2012
PubMed

Insights

Cytoskeleton-associated protein 4 (CKAP4) acts as a receptor for antiproliferative factor (APF) in interstitial cystitis. APF triggers CKAP4 phosphorylation and nuclear translocation, revealing its role in cellular proliferation control.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cytoskeleton-associated protein 4 (CKAP4) is a transmembrane protein involved in cellular processes.
  • CKAP4 is reversibly palmitoylated and phosphorylated, and acts as a receptor for antiproliferative factor (APF).
  • APF is secreted by bladder epithelial cells in patients with interstitial cystitis (IC) and its signaling mechanism via CKAP4 is not fully understood.

Purpose of the Study:

  • To elucidate the mechanism of APF signal transduction mediated by CKAP4.
  • To investigate the role of CKAP4 phosphorylation and localization in response to APF.
  • To determine if CKAP4 functions as a downstream effector of APF.

Main Methods:

  • Investigated APF-induced serine phosphorylation of CKAP4 at specific residues (S3, S17, S19).
  • Examined the nuclear translocation of CKAP4 upon APF treatment.
  • Assessed the binding of CKAP4 to genomic DNA (gDNA) in a phosphorylation-dependent manner.
  • Utilized a phosphomimicking, nonpalmitoylated CKAP4 mutant to study its cellular effects.

Main Results:

  • APF treatment induced serine phosphorylation of CKAP4 at S3, S17, and S19.
  • APF stimulation led to the nuclear translocation of CKAP4.
  • CKAP4 demonstrated phosphorylation-dependent binding to gDNA following APF treatment.
  • A constitutively nonpalmitoylated yet phosphomimicking CKAP4 mutant localized to the nucleus, bound DNA, and inhibited cellular proliferation, mimicking APF's effects.

Conclusions:

  • CKAP4 is a key mediator of APF signal transduction.
  • CKAP4 phosphorylation and nuclear translocation are critical events in APF signaling.
  • CKAP4 plays a novel role as a downstream effector of APF, influencing cellular proliferation.

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