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KMID : 0620920180500050065
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Experimental & Molecular Medicine
2018 Volume.50 No. 5 p.65 ~ p.65
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Modulation of store-operated calcium entry and nascent adhesion by p21-activated kinase 1
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Jeon In-Sook
Kim Hye-Ryun
Shin Eun-Young
Kim Eung-Gook
Han Heon-Seok
Hong Jin-Tae
Lee Hak-Kyo
Song Ki-Duk
Choi Joong-Kook
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Abstract
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Calcium mobilization is necessary for cell movement during embryonic development, lymphocyte synapse formation, wound healing, and cancer cell metastasis. Depletion of calcium in the lumen of the endoplasmic reticulum using inositol triphosphate (IP3) or thapsigargin (TG) is known to induce oligomerization and cytoskeleton-mediated translocation of stromal interaction molecule 1 (STIM1) to the plasma membrane, where it interacts with the calcium release-activated calcium channel Orai1 to mediate calcium influx; this process is referred to as store-operated calcium entry (SOCE). Furthermore, aberrant STIM1 or SOCE regulation is associated with cancer cell motility and metastasis. The p21-activated kinases (PAKs), which are downstream effectors of GTPases, reportedly regulate cytoskeletal organization, protrusive activity, and cell migration. Although cytoskeletal remodeling apparently contributes to calcium mobilization via SOCE, and vice versa, the mechanisms by which they regulate each other remain unclear. In this study, we aimed to characterize whether PAK1 modulates calcium mobilization and STIM1 localization. Our data demonstrate that PAK1 interacts with STIM1 in vitro and that this interaction was enhanced by treatment with a nascent adhesion inducer, such as phorbol 12,13-dibutyrate (PDBu). Under basal conditions, both proteins appeared to primarily colocalize in the cytosol, whereas treatment with PDBu induced their colocalization to vinculin-positive peripheral adhesions. Downregulation of PAK1 activity via chemical inhibitors or by PAK1 shDNA expression impaired STIM1-mediated calcium mobilization via SOCE. Based on these findings, we propose that PAK1 interacts with STIM1 to regulate calcium mobilization and the formation of cellular adhesions.
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KEYWORD
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Calcium signalling, Focal adhesion
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