Calcium signals act as universal second messengers that trigger many cellular processes in both animals and plants, but how specific calcium signals are generated is not well understood. In this study, we determined that AtANNEXIN4, a putative calcium-permeable transporter, and its interacting proteins, SCaBP8 and SOS2, generate a calcium signal under salt stress, which initially activates the Salt Overly Sensitive (SOS) pathway, a conserved mechanism that modulates ion homeostasis in plants under salt stress. After activation, SCaBP8 promotes the interaction of the protein kinase SOS2 with AtANN4, which enhances its phosphorylation by SOS2. This phosphorylation of AtANN4 further increases its interaction with SCaBP8. Both the interaction with and phosphorylation of AtANN4 repress its activity and alter calcium transients and signatures. Our results reveal how downstream targets are required to create a specific calcium signal via a negative feedback regulatory loop, thereby enhancing our understanding of the regulation of calcium signaling.