IP3KC ELISA Kit

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 co-immunoprecipitation 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.

Purpose: Kawasaki disease (KD) is an acute systemic vasculitis. Both the etiology of KD and the erythema of Bacille Calmette-Guerin (BCG) injection sites observed in the disease are poorly understood. We investigated the association between KD and single nucleotide polymorphisms (SNPs) in two candidate genes: inositol 1,4,5-triphosphate 3-kinase (ITPKC), a well-studied KD-associated gene, and solute carrier 11a1 (SLC11A1), which is associated with the hypersensitive reaction to the BCG strain in Koreans. Materials and Methods: Associations between KD and SNPs in two genes were evaluated. Potential associations between BCG injection site erythema and SNPs in two genes were also evaluated. Gene-gene interactions between ITPKC and SLC11A1 in KD and BCG injection site erythema were also analyzed. Results: Three tagging SNPs in ITPKC and five tagging SNPs in SLC11A1 were genotyped in 299 KD patients and 210 control children. SNP rs28493229 in ITPKC was associated with KD and coronary artery complications. SNP rs77624405 in SLC11A1 was associated with KD. Comparisons of KD patients with and without BCG injection site erythema revealed that SNP rs17235409 in SLC11A1 was associated with erythema; no erythema-associated SNPs in ITPKC were identified. Interactions between ITPKC rs28493229_GG and SLC11A1 rs17235409_GA and between ITPKC rs10420685_GG and SLC11A1 rs17235409_AA were strongly associated with BCG injection site erythema. Conclusion: This study identified several important polymorphisms in the ITPKC and SLC11A1 genes in Koreans. The genetic variants identified in this study affected KD and erythema of BCG injection sites independently and through gene-gene interactions. Also, the effects of the polymorphisms were age-dependent.