Okadaic acid mimics the action of insulin in stimulating protein kinase activity in isolated adipocytes. The role of protein phosphatase 2a in attenuation of the signal.

Haystead, Timothy; Weiel, James E.; Litchfield, David W.; Tsukitani, Yasumasa; Fischer, Edmond H.; Krebs, Edwin G.

doi:10.1016/s0021-9258(17)46261-2

Cited by 177 publications

(21 citation statements)

References 58 publications

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“…The finding that PP2A is the major enzyme that inactivates MAPKK in vivo is supported by other evidence. For example, incubation of rat adipocytes with okadaic acid triggers the activation of MAPKK in vivo [26], and MAPKK is activated when the small-T antigen of simian virus 40 is transiently expressed in CV-1 cells [27]. Small-T antigen binds to the A subunit of PP2A and this seems to compromise the ability of the phosphatase to inactivate MAPKK, probably by exchanging with the 55 kD B(x subunit.…”

Section: Identification Of Pp2a As the Major Phosphatase Acting On P42mapk And Mapkk In Extracts From Unstimulated Pc12 Cellsmentioning

confidence: 99%

“…To measure p42mapk phosphatase activities, PC12 cells were lysed in 02 ml ice-cold Buffer A, centrifuged for 5 min at 14 000 x g, and the lysates assayed for protein phosphatase activities by the release of trichloroacetic acid-soluble 32 P-radioactivity from the proteins [37], or after extraction of the phosphate-molybdate complex into isobutanol/heptane [26]. The latter procedure establishes that the released 32 p_ radioactivity is present as orthophosphate and not as small phosphopeptides produced by the action of proteinases.…”

Section: Assay Of Map Kinase and Map Kinase Kinasementioning

confidence: 99%

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Inactivation of p42 MAP kinase by protein phosphatase 2A and a protein tyrosine phosphatase, but not CL100, in various cell lines

et al. 1995

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Section: Identification Of Pp2a As the Major Phosphatase Acting On P42mapk And Mapkk In Extracts From Unstimulated Pc12 Cellsmentioning

confidence: 99%

Section: Assay Of Map Kinase and Map Kinase Kinasementioning

confidence: 99%

Inactivation of p42 MAP kinase by protein phosphatase 2A and a protein tyrosine phosphatase, but not CL100, in various cell lines

et al. 1995

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“…Evidence has suggested that PP2A serves complicated stimulatory and inhibitory roles in growth-and hormone-factor signaling, especially in the extracellular signal-regulated ERK/MAPK cascade and in the activity of ubiquitous intermediary messengers during mitosis (64). PP2A appears to be involved in controlling the activity of maturation-promoting factor (MPF) (65,66) and the modulation of MAP-ERK kinase activity (67,68). Normal kidney development, beginning at embryonic day 12 (E12) in rats and during the 5th gestational week in humans, is strictly regulated and involves several crucial steps in order to achieve a predetermined number of functioning nephrons (39).…”

Section: Pp2a In Renal Developmentmentioning

confidence: 99%

Role of protein phosphatase 2A in kidney disease (Review)

Shao

Fang

et al. 2021

Exp Ther Med

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Kidney disease affects millions of people worldwide and is a financial burden on the healthcare system. Protein phosphatase 2A (PP2A), which is involved in renal development and the function of ion-transport proteins, aquaporin-2 and podocytes, is likely to serve an important role in renal processes. PP2A is associated with the pathogenesis of a variety of different kidney diseases including podocyte injury, inflammation, tumors and chronic kidney disease. The current review aimed to discuss the structure and function of PP2A subunits in the context of kidney diseases. How dysregulation of PP2A in the kidneys causes podocyte death and the inactivation of PP2A in renal carcinoma tissues is discussed. Inhibition of PP2A activity prevents epithelial-mesenchymal transition and attenuates renal fibrosis, creating a favorable inflammatory microenvironment and promoting the initiation and progression of tumor pathogenesis. The current review also indicates that PP2A serves an important role in protection against renal inflammation. Understanding the detailed mechanisms of PP2A provides information that can be utilized in the design and application of novel therapeutics for the treatment and prevention of renal diseases.

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“…Okadaic acid, a polyether fatty acid isolated from the black sponge Halichondria okadai , is a potent inhibitor of both type-1 and type-2 phosphatases (1,2). It has been a useful tool for studying the biological significance of serine/ threonine protein phosphorylation due to its ability to activate S 6 kinase and the mitogen-activated protein kinases (3)(4)(5)(6) and to inhibit phosphatidylinositol 3'-kinase-mediated tyrosine kinase-dependent signal transduction. (7,8).…”

mentioning

confidence: 99%

Mechanism of the stimulatory action of okadaic acid on lipolysis in rat fat cells

Morimoto

Kiyama

Kameda

et al. 2000

Journal of Lipid Research

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Okadaic acid was found to induce concentrationand time-dependent lipolysis in rat fat cells in the absence of lipolytic hormones, but it did not significantly increase the total hormone-sensitive lipase (HSL) activity in these fat cells, the activity of HSL extracted from fat layer and that of HSL in the supernatant of homogenized fat cells. Western blotting of fat cell homogenate fractions with an antiserum raised against synthetic peptide derived from rat HSL showed that HSL protein shifted from the supernatant to the fat layer in response to okadaic acid, which increased the HSL protein content on the fat layer and concomitantly reduced that of the supernatant, concentration-and timedependently. Sonication of the fat cells abolished their responsiveness to okadaic acid. The lipolytic action of okadaic acid was examined and its site was identified using a cell-free system comprising lipid droplets isolated from rat fat cells and HSL. Okadaic acid induced lipolysis in this cell-free system and sonication of the lipid droplets caused disappearance of lipolytic action of okadaic acid. Okadaic acid failed to stimulate lipolysis in a cell-free system comprising HSL and artificial lipid droplets (trioleoylglycerol emulsified with gum arabic) instead of lipid droplets isolated from rat fat cells. These results suggest that okadaic acid does not increase the catalytic activity of HSL but induces translocation of HSL to the lipid droplets isolated from rat fat cells. The site of the lipolytic action of okadaic acid in relation to the interaction between HSL and lipid droplet is discussed. -Morimoto, C., A. Kiyama, K. Kameda, H. Ninomiya, T. Tsujita, and H. Okuda. Mechanism of the stimulatory action of okadic acid on lipolysis in rat fat cells.

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Okadaic acid mimics the action of insulin in stimulating protein kinase activity in isolated adipocytes. The role of protein phosphatase 2a in attenuation of the signal.

Cited by 177 publications

References 58 publications

Inactivation of p42 MAP kinase by protein phosphatase 2A and a protein tyrosine phosphatase, but not CL100, in various cell lines

Inactivation of p42 MAP kinase by protein phosphatase 2A and a protein tyrosine phosphatase, but not CL100, in various cell lines

Role of protein phosphatase 2A in kidney disease (Review)

Mechanism of the stimulatory action of okadaic acid on lipolysis in rat fat cells

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