PMID- 29780159
OWN - NLM
STAT- MEDLINE
DCOM- 20190318
LR  - 20200306
IS  - 2092-6413 (Electronic)
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 50
IP  - 5
DP  - 2018 May 21
TI  - Modulation of store-operated calcium entry and nascent adhesion by p21-activated 
      kinase 1.
PG  - 1-10
LID - 10.1038/s12276-018-0093-2 [doi]
LID - 65
AB  - 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.
FAU - Jeon, In-Sook
AU  - Jeon IS
AD  - Division of Biochemistry, Chungbuk National University, City of Cheongju, 
      361-763, Korea.
FAU - Kim, Hye-Ryun
AU  - Kim HR
AD  - Division of Biochemistry, Chungbuk National University, City of Cheongju, 
      361-763, Korea.
FAU - Shin, Eun-Young
AU  - Shin EY
AD  - Division of Biochemistry, Chungbuk National University, City of Cheongju, 
      361-763, Korea.
FAU - Kim, Eung-Gook
AU  - Kim EG
AD  - Division of Biochemistry, Chungbuk National University, City of Cheongju, 
      361-763, Korea.
FAU - Han, Heon-Seok
AU  - Han HS
AD  - Department of Pediatrics, College of Medicine, Chungbuk National University, City 
      of Cheongju, 361-763, Korea.
FAU - Hong, Jin-Tae
AU  - Hong JT
AD  - College of Pharmacy and Medical Research Center, Chungbuk National University, 
      City of Cheongju, 361-763, Korea.
FAU - Lee, Hak-Kyo
AU  - Lee HK
AD  - Department of Animal Biotechnology, Chonbuk National University, Jeonju-si, 
      Jeollabuk-do, 54896, Korea.
FAU - Song, Ki-Duk
AU  - Song KD
AUID- ORCID: 0000-0003-2827-0873
AD  - Department of Animal Biotechnology, Chonbuk National University, Jeonju-si, 
      Jeollabuk-do, 54896, Korea. kiduk.song@gmail.com.
FAU - Choi, Joong-Kook
AU  - Choi JK
AD  - Division of Biochemistry, Chungbuk National University, City of Cheongju, 
      361-763, Korea. jkchoi@chungbuk.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180521
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (Neoplasm Proteins)
RN  - 0 (STIM1 protein, human)
RN  - 0 (Stromal Interaction Molecule 1)
RN  - 125361-02-6 (Vinculin)
RN  - EC 2.7.11.1 (p21-Activated Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/*metabolism
MH  - Cell Adhesion
MH  - Cell Surface Extensions/metabolism
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Intracellular Space/metabolism
MH  - Neoplasm Proteins/metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Stromal Interaction Molecule 1/metabolism
MH  - Vinculin/metabolism
MH  - p21-Activated Kinases/*metabolism
PMC - PMC5960643
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/05/22 06:00
MHDA- 2019/03/19 06:00
PMCR- 2018/05/21
CRDT- 2018/05/22 06:00
PHST- 2017/08/14 00:00 [received]
PHST- 2018/03/13 00:00 [accepted]
PHST- 2018/02/13 00:00 [revised]
PHST- 2018/05/22 06:00 [entrez]
PHST- 2018/05/22 06:00 [pubmed]
PHST- 2019/03/19 06:00 [medline]
PHST- 2018/05/21 00:00 [pmc-release]
AID - 10.1038/s12276-018-0093-2 [pii]
AID - 93 [pii]
AID - 10.1038/s12276-018-0093-2 [doi]
PST - epublish
SO  - Exp Mol Med. 2018 May 21;50(5):1-10. doi: 10.1038/s12276-018-0093-2.