Protein kinase C phosphorylates the inositol 1,4,5-trisphosphate o

uille represent an interesting model to study this particular isoform. epidermal growth factor, two agonists that use different receptor also in store operated Ca2C entry, a process whereby the In mammalian cells, three subtypes of IP Rs (IP R-1, 3 form different populations of homo- and hetero-tetrameric established for homo-tetrameric channels and much less so 659Journal of Endocrinology (2007) 192, 659–6683 3 IP3R-2 and IP3R-3), derived from three distinct genes, have been identified but the actual role of each subtype in physiological Ca2C signalling remains to be established for hetero-tetrameric channels. It is therefore important to characterize the specific pharmacological properties and the regulatory mechanisms of each IP3R subtype. DOI: 10.1677/JOE-06-0179depletion of intracellular Ca2C store causes the opening of Ca2C channels in the plasma membrane (for review see Smyth et al. 2006). The elevation of cytosolic free Ca2C concentration is a dynamic signal regulating a variety of important cellular functions such as secretion, contraction, metabolism and gene transcription (Berridge et al. 2003). channels (Joseph et al. 1995, Monkawa et al. 1995, Wojcikiewicz &He 1995, Nucifora et al. 1996). The relatively poor homology between the regulatory domains of the three IP3Rs subtypes is likely to confer specific pharmacological and functional properties to each subtype. The functional significance of subtype diversity has not been clearlytheir opening liberates stored Ca2C that diffuses in the cytosol and triggers Ca2C-dependent cellular responses. IP3Rs play major roles in agonists-induced intracellular Ca2C release and 1999, Patterson et al. 2004). IP3Rs associate in tetrameric structures that form functional Ca2C channels. Individual cell types can express more than one IP R subtype, which maykinase C (PKC) influences IP3R-2-mediated Ca release. Using an immunoprecipitation approach, we confirmed that AR4-2J cells express almost exclusively the IP3R-2 isoform. Using an in vitro phosphorylation assay, we showed that th