PPP3CC feedback regulates IP3-Ca2+ pathway through preventing ITPKC degradation

Pu Li, Peng Zhang, Ying Lin, Jingxuan Shan, Jiaqi Wang, Tong Zhou, Zhenggang Zhu, Keke Huo

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

ITPKC, a susceptibility gene of Kawasaki disease, encodes a kinase that negatively regulates intracellular Ca2+ level and inhibits calcineurin-dependent activation of NFAT by phosphorylating IP3. In this study, we identified a novel ITPKC-interacting protein, namely PPP3CC, using yeast two-hybrid. This interaction was further confirmed by GST pull-down and coimmunoprecipitation assays, and fluorescent microscopy showed co-localization of both proteins in the cell cytoplasm. Our functional studies demonstrated that PPP3CC positively influences the protein level of ITPKC, likely by inhibiting phosphorylation of ITPKC and consequently preventing ITPKC from ubiquitin-mediated protein degradation which requires phosphorylation. Importantly, the protein level of PPP3CC negatively correlates with the cellular level of IP3, suggesting a regulatory role of PPP3CC in the IP3-Ca2+ signaling pathway.

Original languageEnglish
Pages (from-to)919-927
Number of pages9
JournalFrontiers in Bioscience
Volume18
Issue number3
DOIs
Publication statusPublished - 1 Jun 2013
Externally publishedYes

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Feedback
Degradation
Phosphorylation
Proteins
Mucocutaneous Lymph Node Syndrome
Calcineurin
Ubiquitin
Proteolysis
Microscopy
Cytoplasm
Phosphotransferases
Yeasts
Yeast
Assays
Microscopic examination
Genes
Chemical activation

Keywords

  • IP3-ca2+ signal
  • ITPKC
  • Kawasaki disease
  • PPP3CC
  • Protein interaction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

PPP3CC feedback regulates IP3-Ca2+ pathway through preventing ITPKC degradation. / Li, Pu; Zhang, Peng; Lin, Ying; Shan, Jingxuan; Wang, Jiaqi; Zhou, Tong; Zhu, Zhenggang; Huo, Keke.

In: Frontiers in Bioscience, Vol. 18, No. 3, 01.06.2013, p. 919-927.

Research output: Contribution to journalArticle

Li, P, Zhang, P, Lin, Y, Shan, J, Wang, J, Zhou, T, Zhu, Z & Huo, K 2013, 'PPP3CC feedback regulates IP3-Ca2+ pathway through preventing ITPKC degradation', Frontiers in Bioscience, vol. 18, no. 3, pp. 919-927. https://doi.org/10.2741/4153
Li, Pu ; Zhang, Peng ; Lin, Ying ; Shan, Jingxuan ; Wang, Jiaqi ; Zhou, Tong ; Zhu, Zhenggang ; Huo, Keke. / PPP3CC feedback regulates IP3-Ca2+ pathway through preventing ITPKC degradation. In: Frontiers in Bioscience. 2013 ; Vol. 18, No. 3. pp. 919-927.
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