STIM1 has been recently identified as a Ca 2؉ sensor in endoplasmic reticulum (ER) and an initiator of the store-operated Ca 2؉ entry (SOCE) pathway, but the mechanism of SOCE activation remains controversial. Here we focus on the early ERdelimited steps of the SOCE pathway and demonstrate that STIM1 is critically involved in initiating of production of calcium influx factor (CIF), a diffusible messenger that can deliver the signal from the stores to plasma membrane and activate SOCE. We discovered that CIF production is tightly coupled with STIM1 expression and requires functional integrity of its intraluminal sterile ␣-motif (SAM) domain. We demonstrate that 1) molecular knockdown or overexpression
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.