Phosphorylation-mediated structural changes within the SOAR domain of stromal interaction molecule 1 enable specific activation of distinct Orai channels.

Thompson, J.; Lai-Zhao, Yue; Stathopulos, Peter B.; Grossfield, Alan; Shuttleworth, Trever J.

doi:10.1074/jbc.aac118.004562

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“…Orai1 is trapped within these puncta (Liou et al , ) and STIM1 binds to Orai1 via the OASF (AA 233–474), which consists of the CC1 domain (CC1α1, CC1α2, and CC1α3) and two additional coiled‐coil domains (CC2 and CC3). Phosphorylation of STIM1 in its CC2 domain, at Y361 or T389, promotes STIM1 interaction with Orai1 and SOCE (Yazbeck et al , ; Thompson et al , ). Additionally, phosphorylation of a cluster of sites close to or within the serine/proline‐rich domain near the PM interaction region (S572, S575, S608, and S621) promotes STIM1 interaction with Orai1 (Pozo‐Guisado et al , ; Casas‐Rua et al , ).…”

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confidence: 99%

Phosphoproteomics reveals conserved exercise‐stimulated signaling and AMPK regulation of store‐operated calcium entry

et al. 2019

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Exercise stimulates cellular and physiological adaptations that are associated with widespread health benefits. To uncover conserved protein phosphorylation events underlying this adaptive response, we performed mass spectrometry‐based phosphoproteomic analyses of skeletal muscle from two widely used rodent models: treadmill running in mice and in situ muscle contraction in rats. We overlaid these phosphoproteomic signatures with cycling in humans to identify common cross‐species phosphosite responses, as well as unique model‐specific regulation. We identified > 22,000 phosphosites, revealing orthologous protein phosphorylation and overlapping signaling pathways regulated by exercise. This included two conserved phosphosites on stromal interaction molecule 1 (STIM1), which we validate as AMPK substrates. Furthermore, we demonstrate that AMPK‐mediated phosphorylation of STIM1 negatively regulates store‐operated calcium entry, and this is beneficial for exercise in Drosophila. This integrated cross‐species resource of exercise‐regulated signaling in human, mouse, and rat skeletal muscle has uncovered conserved networks and unraveled crosstalk between AMPK and intracellular calcium flux.

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