Open Access

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

Pu Li1,2,Peng Zhang3,Ying Lin1,Jingxuan Shan4,Jiaqi Wang1,Tong Zhou2,Zhenggang Zhu2,Keke Huo1,*
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 220 Handan Rd., Shanghai 200433, PR China
Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University, 197 Rui Jin Er Rd, Shanghai 200025, PR China
Department of Thoracic Surgery, Shanghai Pulmonary Hospital of Tongji University,507 Zhengmin Rd., Shanghai 200433, PR China
Laboratory of Genetic Medcine and Immunology, Weill Cornell Medical College in Qatar – Qatar Foundation, Education City, P.O.Box 24144, Doha, Qatar
DOI: 10.2741/4153 Volume 18 Issue 3, pp.919-927
Published: 01 June 2013
*Corresponding Author(s):  
Keke Huo

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.

Key words

ITPKC, PPP3CC, IP3-Ca2+ signal, Kawasaki disease, Protein interaction

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Pu Li, Peng Zhang, Ying Lin, Jingxuan Shan, Jiaqi Wang, Tong Zhou, Zhenggang Zhu, Keke Huo. PPP3CC feedback regulates IP3-Ca2+ pathway through preventing ITPKC degradation. Frontiers in Bioscience-Landmark. 2013. 18(3); 919-927.