Abstract
In the human neuroblastoma SH-SY5Y cell line, the glutathione transferase Omega 1-1 (GSTO1-1) appears to modulate Akt and MEK1/2 kinase activation. We observed a glutathionylation modification was involved in the activation of Akt but not MEK1/2. With the specific GSTO1-1 inhibitor ML175, we show the enzyme activity of GSTO1-1 is important for modulation as the inhibited GSTO1-1 allowed activation of both Akt and MEK1/2. The inhibition of GSTO1-1 showed a similar extent of activation of Akt and MEK1/2 as treatment by the endotoxin lipopolysaccharide. The GSTO1-1 also either directly interacts with Akt and MEK1/2 or interacts with a protein complexed with Akt and MEK1/2 as both kinases coimmunoprecipitated with GSTO1-1. The results suggest that GSTO1-1 enzyme activity inhibits the activation of these two kinases to maintain basal levels. The possible regulation by GSTO1-1 is of interest as both kinases have hundreds of potential downstream targets that are known to have contributions to various cellular processes including survival, growth, proliferation, and metabolism.
| Original language | English |
|---|---|
| Pages (from-to) | 588-595 |
| Number of pages | 8 |
| Journal | Proteins: Structure, Function and Bioinformatics |
| Volume | 87 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 2019 |
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Keywords
- Akt/PKB
- glutathione transferase (GST)
- glutathionylation
- MEK1/2
- ML175
ASJC Scopus subject areas
- Structural Biology
- Biochemistry
- Molecular Biology
Cite this
Glutathione transferase Omega 1-1 (GSTO1-1) modulates Akt and MEK1/2 signaling in human neuroblastoma cell SH-SY5Y. / Saisawang, Chonticha; Wongsantichon, Jantana; Robinson, Robert C.; Ketterman, Albert J.
In: Proteins: Structure, Function and Bioinformatics, Vol. 87, No. 7, 07.2019, p. 588-595.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glutathione transferase Omega 1-1 (GSTO1-1) modulates Akt and MEK1/2 signaling in human neuroblastoma cell SH-SY5Y
AU - Saisawang, Chonticha
AU - Wongsantichon, Jantana
AU - Robinson, Robert C.
AU - Ketterman, Albert J.
PY - 2019/7
Y1 - 2019/7
N2 - In the human neuroblastoma SH-SY5Y cell line, the glutathione transferase Omega 1-1 (GSTO1-1) appears to modulate Akt and MEK1/2 kinase activation. We observed a glutathionylation modification was involved in the activation of Akt but not MEK1/2. With the specific GSTO1-1 inhibitor ML175, we show the enzyme activity of GSTO1-1 is important for modulation as the inhibited GSTO1-1 allowed activation of both Akt and MEK1/2. The inhibition of GSTO1-1 showed a similar extent of activation of Akt and MEK1/2 as treatment by the endotoxin lipopolysaccharide. The GSTO1-1 also either directly interacts with Akt and MEK1/2 or interacts with a protein complexed with Akt and MEK1/2 as both kinases coimmunoprecipitated with GSTO1-1. The results suggest that GSTO1-1 enzyme activity inhibits the activation of these two kinases to maintain basal levels. The possible regulation by GSTO1-1 is of interest as both kinases have hundreds of potential downstream targets that are known to have contributions to various cellular processes including survival, growth, proliferation, and metabolism.
AB - In the human neuroblastoma SH-SY5Y cell line, the glutathione transferase Omega 1-1 (GSTO1-1) appears to modulate Akt and MEK1/2 kinase activation. We observed a glutathionylation modification was involved in the activation of Akt but not MEK1/2. With the specific GSTO1-1 inhibitor ML175, we show the enzyme activity of GSTO1-1 is important for modulation as the inhibited GSTO1-1 allowed activation of both Akt and MEK1/2. The inhibition of GSTO1-1 showed a similar extent of activation of Akt and MEK1/2 as treatment by the endotoxin lipopolysaccharide. The GSTO1-1 also either directly interacts with Akt and MEK1/2 or interacts with a protein complexed with Akt and MEK1/2 as both kinases coimmunoprecipitated with GSTO1-1. The results suggest that GSTO1-1 enzyme activity inhibits the activation of these two kinases to maintain basal levels. The possible regulation by GSTO1-1 is of interest as both kinases have hundreds of potential downstream targets that are known to have contributions to various cellular processes including survival, growth, proliferation, and metabolism.
KW - Akt/PKB
KW - glutathione transferase (GST)
KW - glutathionylation
KW - MEK1/2
KW - ML175
UR - http://www.scopus.com/inward/record.url?scp=85063344312&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063344312&partnerID=8YFLogxK
U2 - 10.1002/prot.25683
DO - 10.1002/prot.25683
M3 - Article
C2 - 30874320
AN - SCOPUS:85063344312
VL - 87
SP - 588
EP - 595
JO - Proteins: Structure, Function and Genetics
JF - Proteins: Structure, Function and Genetics
SN - 0887-3585
IS - 7
ER -