Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Enzyme
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Query: EC:3.1.3.16 (
calcineurin
)
17,112
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Sterol regulatory element-binding protein-1 (SREBP-1) is a key transcription factor in stimulating lipogenesis in the liver.
Protein-tyrosine phosphatase 1B
(
PTP1B
) induces SREBP-1 gene expression via protein phosphatase 2A (
PP2A
) activation.
PTP1B
is reported to be anchored on the endoplasmic reticulum (ER) via its C-terminal tail, and change in intracellular localization of
PTP1B
by C-terminal-truncation did not alter its inhibitory effects on insulin signaling. In this study, we investigated whether the change in intracellular localization of
PTP1B
could influence SREBP-1 gene expression. Overexpression of C-terminal truncated
PTP1B
(PTP1BdeltaCT) in rat Fao cells did not induce SREBP-1 gene expression. Furthermore, PTP1BdeltaCT failed to bind
PP2A
, resulting in impaired
PP2A
activation, whereas overexpression of wild-type
PTP1B
(PTP1BWT) associated with
PP2A
. Moreover, a membrane-targeted PTP1BDeltaCT activated
PP2A
with restored
PP2A
binding, despite the absence of its C-terminal region. Finally, overexpression of PTP1BdeltaCT into mouse primary cultured hepatocytes failed to enhance SREBP-1c mRNA, whereas membrane-targeted PTP1BdeltaCT led to enhanced SREBP-1c mRNA in hepatocytes as well as PTP1BWT. In conclusion, membrane localization of
PTP1B
is essential for
PP2A
activation, which is crucial for its enhancement of SREBP-1 gene expression.
...
PMID:Membrane localization of protein-tyrosine phosphatase 1B is essential for its activation of sterol regulatory element-binding protein-1 gene expression. 1789 22
Protein-tyrosine phosphatase 1B
(
PTP1B
) is a major regulator of insulin sensitivity. We have described a novel action of
PTP1B
in the induction of sterol regulatory element-binding protein-1 (SREBP-1) gene expression through activation of protein phosphatase 2A (
PP2A
).
PTP1B
is anchored to the endoplasmic reticulum membrane via its C-terminal tail. We have previously reported that membrane localization of
PTP1B
is essential for
PP2A
activation, which is crucial for enhancing SREBP-1 gene expression in in vitro experiments. In this study, we further investigated the physiological importance of membrane localization of
PTP1B
in vivo. We found that transient liver-specific overexpression of wild-type
PTP1B
(PTP1B-WT) using adenovirus-mediated gene transfer was associated with hypertriglyceridaemia and enhanced hepatic SREBP-1 gene expression in mice. However, overexpression of the C-terminal truncated
PTP1B
(PTP1BDeltaCT) failed to increase hepatic SREBP-1 expression or serum triglyceride levels, despite causing insulin resistance. Our results indicate that activation of
PTP1B
in the liver could induce hypertriglyceridaemia and that anchoring of
PTP1B
to the membrane is crucial for its action.
...
PMID:Membrane localization of protein-tyrosine phosphatase 1B is essential for its activation of sterol regulatory element-binding protein-1 gene expression and consequent hypertriglyceridaemia. 1960 64
