Genes involved in the unfolded protein response (UPR) differ in transiently versus sustained gastrin treated cells. A: Schematic presentation of the three signalling pathways initiated by the stress sensors IRE1, PERK and ATF6 in the UPR. The green circles indicate genes differentially expressed in transiently versus sustained gastrin treated cells. IRE1, PERK and ATF6 are associated with the protein chaperone BiP (HSPA5/GRP78) in their inactive state. In response to stress, unfolded proteins accumulate and bind to BiP, leading to release and activation of the three stress sensors and activation of their respective pathways: IRE1 activates and initiates nonconventional splicing of Xbp1 mRNA. PERK phosphorylates eIF2α leading to a general attenuation of translational initiation and a selective induction of ATF4 translation. ATF6 transits to the Golgi where it is cleaved to yield a cytoplasmic fragment which moves into the nucleus. XBP1, ATF4 and ATF6 activate a wide variety of UPR target genes, including BiP, Chop, Herp and Chac1 [16, 20, 21]. B: Data from two independent time series microarray experiments showing time profiles for UPR genes differentially expressed in transiently versus sustained gastrin treated cells. Left panels: The data were extracted from a time series experiment where sustained gastrin treated cells were harvested at 10 different time points between 15 min and 14 h. The samples from untreated control cells were harvested at time zero and throughout the time course (11 time points). The mRNA expression level for untreated (open dots) and sustained gastrin treated (black dots) cells are shown as normalized log2-transformed signal intensities (N=2). Right panels: Gastrin induced gene expression in transiently (grey lines) and sustained (black lines) treated cells (stimulation protocol presented in Figure 1). The data is shown as mean fold induction relative to untreated cells at the same time point (N=2).