PMID- 30587575
OWN - NLM
STAT- MEDLINE
DCOM- 20190506
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 294
IP  - 9
DP  - 2019 Mar 1
TI  - O-GlcNAcylation regulates integrin-mediated cell adhesion and migration via 
      formation of focal adhesion complexes.
PG  - 3117-3124
LID - 10.1074/jbc.RA118.005923 [doi]
AB  - O-GlcNAcylation is a post-translational modification of a protein serine or 
      threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and 
      cytoplasm. O-GlcNAcylation plays important roles in the cellular signaling that 
      affect the different biological functions of cells, depending upon cell type. 
      However, whether or not O-GlcNAcylation regulates cell adhesion and migration 
      remains unclear. Here, we used the doxycycline-inducible short hairpin RNA 
      (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that 
      O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal 
      adhesion (FA) complex formation. The expression levels of OGT and O-GlcNAcylation 
      were remarkably suppressed 24 h after induction of doxycycline. Knockdown of OGT 
      significantly promoted cell adhesion, but it suppressed the cell migration on 
      fibronectin. The immunostaining with paxillin, a marker for FA plaque, clearly 
      showed that the number of FAs was increased in the KD cells compared with that in 
      the control cells. The O-GlcNAcylation levels of paxillin, talin, and focal 
      adhesion kinase were down-regulated in KD cells. Interestingly, the complex 
      formation between integrin beta1, focal adhesion kinase, paxillin, and talin was 
      greatly increased in KD cells. Consistently, levels of active integrin beta1 were 
      significantly enhanced in KD cells, whereas they were decreased in cells 
      overexpressing OGT. The data suggest a novel regulatory mechanism for 
      O-GlcNAcylation during FA complex formation, which thereby affects integrin 
      activation and integrin-mediated functions such as cell adhesion and migration.
CI  - (c) 2019 Xu et al.
FAU - Xu, Zhiwei
AU  - Xu Z
AD  - From the Division of Regulatory Glycobiology, Institute of Molecular Biomembrane 
      and Glycobiology, Tohoku Medical and Pharmaceutical University, 4-4-1 
      Komatsushima, Aoba-ku, Sendai Miyagi 981-8558, Japan and.
FAU - Isaji, Tomoya
AU  - Isaji T
AD  - From the Division of Regulatory Glycobiology, Institute of Molecular Biomembrane 
      and Glycobiology, Tohoku Medical and Pharmaceutical University, 4-4-1 
      Komatsushima, Aoba-ku, Sendai Miyagi 981-8558, Japan and.
FAU - Fukuda, Tomohiko
AU  - Fukuda T
AD  - From the Division of Regulatory Glycobiology, Institute of Molecular Biomembrane 
      and Glycobiology, Tohoku Medical and Pharmaceutical University, 4-4-1 
      Komatsushima, Aoba-ku, Sendai Miyagi 981-8558, Japan and.
FAU - Wang, Yuqin
AU  - Wang Y
AD  - the Department of Pharmacology, Pharmacy College, Nantong University, Nantong, 
      Jiangsu Province 226001, China.
FAU - Gu, Jianguo
AU  - Gu J
AD  - From the Division of Regulatory Glycobiology, Institute of Molecular Biomembrane 
      and Glycobiology, Tohoku Medical and Pharmaceutical University, 4-4-1 
      Komatsushima, Aoba-ku, Sendai Miyagi 981-8558, Japan and jgu@tohoku-mpu.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181226
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Integrin beta1)
RN  - 0 (Paxillin)
RN  - 0 (Talin)
RN  - EC 2.4.1.- (N-Acetylglucosaminyltransferases)
RN  - EC 2.4.1.- (O-GlcNAc transferase)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (PTK2 protein, human)
RN  - V956696549 (Acetylglucosamine)
SB  - IM
MH  - Acetylglucosamine/*metabolism
MH  - *Cell Adhesion
MH  - *Cell Movement
MH  - Focal Adhesion Kinase 1/metabolism
MH  - Focal Adhesions/*metabolism
MH  - Gene Knockdown Techniques
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Integrin beta1/*metabolism
MH  - N-Acetylglucosaminyltransferases/deficiency/genetics/*metabolism
MH  - Paxillin/metabolism
MH  - *Protein Processing, Post-Translational
MH  - Talin/metabolism
PMC - PMC6398131
OTO - NOTNLM
OT  - O-GlcNAcylation
OT  - O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT)
OT  - cell adhesion
OT  - cell migration
OT  - focal adhesions
OT  - glycosylation
OT  - integrin
COIS- The authors declare that they have no conflicts of interest with the contents of 
      this article
EDAT- 2018/12/28 06:00
MHDA- 2019/05/07 06:00
PMCR- 2020/03/01
CRDT- 2018/12/28 06:00
PHST- 2018/09/19 00:00 [received]
PHST- 2018/12/02 00:00 [revised]
PHST- 2018/12/28 06:00 [pubmed]
PHST- 2019/05/07 06:00 [medline]
PHST- 2018/12/28 06:00 [entrez]
PHST- 2020/03/01 00:00 [pmc-release]
AID - S0021-9258(20)39246-2 [pii]
AID - RA118.005923 [pii]
AID - 10.1074/jbc.RA118.005923 [doi]
PST - ppublish
SO  - J Biol Chem. 2019 Mar 1;294(9):3117-3124. doi: 10.1074/jbc.RA118.005923. Epub 
      2018 Dec 26.