PHAS‐I phosphorylation in response to foetal bovine serum (FBS) is regulated by an ERK1/ERK2‐independent and rapamycin‐sensitive pathway in 3T3‐L1 adipocytes

Arnott, Caroline H.; Atkinson, P. G. P.; Sale, Elizabeth M.; Sale, Graham J.

doi:10.1016/s0014-5793(97)00266-4

Cited by 8 publications

(10 citation statements)

References 29 publications

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“…In studies of 3T3-L1 cells show C/EBP-ββ and C/EBP-α δ are expressed before and activate the transcription of these master regulators PPAR-γ and C/EBP-α. Several studies have been reported that extracellular signal-regulated kinases (ERK) and Akt pathway play essential roles in adipogenesis [11]–[13]. From these studies showed that ERK1/2 phosphorylation had an important role in early stage of adipocytes differentiation [14].…”

Section: Introductionmentioning

confidence: 99%

Aristolochia Manshuriensis Kom Inhibits Adipocyte Differentiation by Regulation of ERK1/2 and Akt Pathway

et al. 2012

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Aristolochia manshuriensis Kom (AMK) is a traditional medicinal herb used for the treatment of arthritis, rheumatism, hepatitis, and anti-obesity. Because of nephrotoxicity and carcinogenicity of AMK, there are no pharmacological reports on anti-obesity potential of AMK. Here, we showed AMK has an inhibitory effect on adipocyte differentiation of 3T3-L1 cells along with significantly decrease in the lipid accumulation by downregulating several adipocyte-specific transcription factors including peroxisome proliferation-activity receptor γ (PPAR-γ), CCAAT/enhancer binding protein α (C/EBP-α) and C/EBP-β, which are critical for adipogenesis in vitro. AMK also markedly activated the extracellular signal-regulated protein kinase 1/2 (ERK1/2) pathway including Ras, Raf1, and mitogen-activated protein kinase kinase 1 (MEK1), and significantly suppressed Akt pathway by inhibition of phosphoinositide-dependent kinase 1 (PDK1). Aristolochic acid (AA) and ethyl acetate (EtOAc) fraction of AMK with AA were significantly inhibited TG accumulation, and regulated two pathway (ERK1/2 and Akt) during adipocyte differentiation, and was not due to its cytotoxicity. These two pathways were upstream of PPAR-γ and C/EBPα in the adipogenesis. In addition, gene expressions of secreting factors such as fatty acid synthase (FAS), adiponectin, lipopreotein lipase (LPL), and aP2 were significantly inhibited by treatment of AMK during adipogenesis. We used the high-fat diet (HFD)-induced obesity mouse model to determine the inhibitory effects of AMK on obesity. Oral administration of AMK (62.5 mg/kg/day) significantly decreased the fat tissue weight, total cholesterol (TC), and low density lipoprotein-cholesterol (LDL-C) concentration in the blood. The results of this study suggested that AMK inhibited lipid accumulation by the down-regulation of the major transcription factors of the adipogensis pathway including PPAR-γ and C/EBP-α through regulation of Akt pathway and ERK 1/2 pathway in 3T3-L1 adipocytes and HFD-induced obesity mice, and AA may be main act in inhibitory effects of AMK during adipocyte differentiation.

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Section: Introductionmentioning

confidence: 99%

Aristolochia Manshuriensis Kom Inhibits Adipocyte Differentiation by Regulation of ERK1/2 and Akt Pathway

et al. 2012

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“…Together, these results suggest that basal cells possess a constant level of kinase activity that is actively suppressed by the action of PPases. Arnott et al (25) reported that serum-induced PHAS-I phosphorylation is independent of the ERKlERK2 pathway in 3T3-Ll adipocytes. We previously showed (9) that inhibition of MAPK and ~7 0 '~~ greatly reduced Prl-mediated Nb2 protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

Okadaic Acid Mimics Several Proximal Effects of Prolactin in Nb2 Lymphoma Cells

Carey

Liberti

1998

Experimental Biology and Medicine

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We previously reported that prolactin-mediated macromolecular synthesis and mitogenesis are coupled to the activation of mitogen-activated protein kinase (MAPK) and p70 S6-kinase (p70S6K). Full activation of MAPK requires tyrosine and threonine phosphorylation whereas that of p70S6K requires serine phosphorylation. In the present study, okadaic acid, which inhibits serine/threonine protein phosphatase activity, was used to explore the linkage of MAPK and p70S6K activation to down-stream effects of prolactin in Nb2 cells. The results show that 1 nM okadaic acid augmented prolactin-stimulated mitogenesis and synthesis of protein and DNA 250%, 42%, and 70%, respectively. Addition of okadaic acid alone a) stimulated and sustained p70S6K activity (5- to 8-fold) and MAPK (3.5- to 5-fold); and b) increased protein synthesis with the maximum effect being about equal to that of prolactin (2.1-fold with 1 nMokadaic acid versus 2.3-fold with 0.2 nMprolactin). However, okadaic acid did not affect DNA synthesis or mitogenesis. These results indicate that the activation of MAPK and p70S6K is necessary for stimulation of protein synthesis but not sufficient for prolactin-driven mitogenesis.

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“…Activation of the ERK1/ ERK2 cascade is a well established post-receptor response to insulin treatment. The effect of ␣AS1 treatment on insulinstimulated ERK2 activation was measured by band shift on anti-ERK2 Western blots (17). An insulin concentration was chosen that activated Ͻ50% of the cellular ERK2 pool, such that any augmentation in ERK2 activation caused by PTP␣ depletion would be detected.…”

Section: Development and Characterization Of An Antisense Strategy Fomentioning

confidence: 99%

Use of an Antisense Strategy to Dissect the Signaling Role of Protein-tyrosine Phosphatase α

Arnott¹,

Sale

Miller

et al. 1999

Journal of Biological Chemistry

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The protein-tyrosine phosphatase PTP␣ has been proposed to play an important role in controlling the dephosphorylation of a number of key signaling proteins and in regulating insulin signaling. To examine the potential cellular functions and physiological substrates of PTP␣, a potent phosphorothioate oligonucleotide-based antisense strategy was developed that specifically depleted endogenous PTP␣ from 3T3-L1 adipocytes. The antisense probe, ␣AS1, achieved PTP␣ depletion levels normally of >85% and which varied up to levels where PTP␣ was not detected at all. Elimination of PTP␣ by 85% inhibited c-Src activity by 80%. Abolishing PTP␣ to levels undetected did not alter the tyrosine dephosphorylation of the insulin receptor or insulin receptor substrate proteins. Moreover, the ability of insulin to activate ERK2 or to stimulate DNA synthesis was not altered by ␣AS1. It is concluded that endogenous PTP␣ is a key regulator of c-Src activity in 3T3-L1 adipocytes and that PTP␣ is not required for the dephosphorylation of the insulin receptor or the insulin receptor substrate proteins or for the regulation of several downstream insulin signaling events in 3T3-L1 adipocytes. Finally, the development of the antisense probe, ␣AS1, provides an important molecular tool of general applicability for further dissecting the roles and precise targets of endogenous PTP␣.

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PHAS‐I phosphorylation in response to foetal bovine serum (FBS) is regulated by an ERK1/ERK2‐independent and rapamycin‐sensitive pathway in 3T3‐L1 adipocytes

Cited by 8 publications

References 29 publications

Aristolochia Manshuriensis Kom Inhibits Adipocyte Differentiation by Regulation of ERK1/2 and Akt Pathway

Aristolochia Manshuriensis Kom Inhibits Adipocyte Differentiation by Regulation of ERK1/2 and Akt Pathway

Okadaic Acid Mimics Several Proximal Effects of Prolactin in Nb2 Lymphoma Cells

Use of an Antisense Strategy to Dissect the Signaling Role of Protein-tyrosine Phosphatase α

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