PKC-β modulates Ca2+ mobilization through Stim1 phosphorylation.

Hye-Jin Song, In-Sook Jeon, Seung Ryul Kim, Kwan Sik Park, Jae-Won Soh, Kwang Youl Lee, Jae-Cheon Shin, Hak-Kyo Lee, Joong-Kook Choi

Genes & genomics 2022 May

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Calcium ions play a pivotal role in cell proliferation, differentiation, and migration. Under basal conditions, the calcium level is tightly regulated; however, cellular activation by growth factors increase the ion level through calcium pumps in the plasma membrane and endoplasmic reticulum for calcium signaling. Orai1 is a major calcium channel in the cell membrane of non-excitable cells, and its activity depends on the stromal interaction molecule 1 (Stim1). Several groups reported that the store-operated calcium entry (SOCE) can be modulated through phosphorylation of Stim1 by protein kinases such as extracellular signal-regulated kinase (ERK), protein kinase A (PKA), and p21-activated kinase (PAK). PKC is a protein kinase that is activated by calcium and diacylglycerol (DAG), but it remains unclear what role activated PKC plays in controlling the intracellular calcium pool. Here, we investigated whether PKC-β controls intracellular calcium dynamics through Stim1. Several biochemical methods such as immune-precipitation, site directed mutagenesis, in vitro kinase assay were employed to investigate PKC interaction with and phosphorylation of Stim1. Intracellular calcium mobilization, via Stim1 mediated SOCE channel, were studied using in the presence of PKC activator or inhibitor under a confocal microscope. Our data demonstrate that PKC interacts with and phosphorylates Stim1 in vitro. phosphorylation of Stim1 at its C-terminal end appears to be important in the regulation of SOCE activity in HEK293 and HeLa cells. Additionally, transient intracellular calcium mobilization assays demonstrate that the SOCE activity was inhibited by PKC activators or activated by PKC inhibitors. In sum, our data suggest a repressive role of PKC in regulating calcium entry through SOCE. © 2022. The Author(s).

Citation

Hye-Jin Song, In-Sook Jeon, Seung Ryul Kim, Kwan Sik Park, Jae-Won Soh, Kwang Youl Lee, Jae-Cheon Shin, Hak-Kyo Lee, Joong-Kook Choi. PKC-β modulates Ca2+ mobilization through Stim1 phosphorylation. Genes & genomics. 2022 May;44(5):571-582