Interaction of Protein Phosphatases and Ethanol on Phospholipase C‐Mediated Intracellular Signal Transduction Processes in Rat Hepatocytes: Role of Protein Kinase A

Higashi, Katsuyoshi; Hoshino, Makoto; Nomura, Tomoyuki; Saso, Katsuhisa; Itō, Makoto; Hoek, Jan B.

doi:10.1111/j.1530-0277.1996.tb01800.x

Cited by 18 publications

(19 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies showed that Ca 2 * mobilization and IP3 accumulation induced by ethanol and vasopressin in rat hepatocytes were potentiated by cpt-cAMP (Higashi et al, 1996). Agents that increase cAMP levels have no significant effects on basal inositol phosphate synthesis but enhance the effect of AVP-induced IP3 accumulation (Pittner and Fain, 1989a,b).…”

Section: Discussionmentioning

confidence: 99%

“…These studies led to the conclusions that phosphorylation of PLCP-2 and PLCP-3 by PKA could explain the inhibition of Gp v -stimulated PI turnover by cAMP (Liu and Simon, 1996;Ali et al, 1998 and Exton, 1986;Pittner and Fain, 1989a,b;Burgess et al, 1991;Higashi et al, 1996). The Ca 2+ mobilization and IP3 accumulation induced by ethanol and AVP are potentiated by cptcAMP (Higashi et al, 1996), although, agents that increase cAMP levels have no significant effects on basal inositol phosphate formation, but enhance A VP-induced inositol phosphate formation (Pittner and Fain, 1989a,b). Thus, at least two mechanisms might be involved:…”

Section: Inhibition Of Plc Via Pkamentioning

confidence: 99%

“…The heterotrimeric G proteins mediate a variety of cellular processes by coupling transmembrane receptors to different effector molecules, including adenylyl cyclase and phospholipase C- (3 (Simon et al, 1991;Neer, 1995 Interaction between the G protein-PLC pathway and PKA has been documented in numerous studies (Blackmore and Exton, 1986;Pittner and Fain, 1989a,b;Burgess et al, 1991;Rhee and Choi, 1992;Liu and Simon, 1996;Higashi et al, 1996;Rhee and Bae, 1997;Ali et al, 1998;Dodge and Sanborn, 1998;Yue et al, 1998). Although it is generally agreed that PKA can inhibit G protein-activated PLC activity (Rhee and Choi, 1992;Liu and Simon, 1996;Rhee and Bae, 1997;Ali et al, 1998;Dodge and Sanborn, 1998;Yue et al, 1998), it can enhance the G protein-PLC pathway in some cases (Blackmore and Exton, 1986;Pittner and Fain, 1989a,b;Burgess et al, 1991;Higashi et al, 1996).…”

Section: The Interaction Between Pka and Phospholipase C (Plc)mentioning

confidence: 99%

“…Although it is generally agreed that PKA can inhibit G protein-activated PLC activity (Rhee and Choi, 1992;Liu and Simon, 1996;Rhee and Bae, 1997;Ali et al, 1998;Dodge and Sanborn, 1998;Yue et al, 1998), it can enhance the G protein-PLC pathway in some cases (Blackmore and Exton, 1986;Pittner and Fain, 1989a,b;Burgess et al, 1991;Higashi et al, 1996).…”

Section: The Interaction Between Pka and Phospholipase C (Plc)mentioning

confidence: 99%

“…first, PKA potentiates the agonist-induced IP3 formation (Blackmore and Exton, 1986;Pittner and Fain, 1989a,b;Higashi et al, 1996), second, PKA potentiates the Ca 2+ release from sensitive Ca 2+ stores in the cell by making the receptor more responsive to lower levels of IP3 (Burgess et al, 1991).…”

Section: Inhibition Of Plc Via Pkamentioning

confidence: 99%

See 4 more Smart Citations

Arginine vasopressin-induced glucagon release: interaction with glucose and cyclic AMP-dependent protein kinase

Abu-Basha

View full text Add to dashboard Cite

This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer.The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction.In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion.Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand comer and continuing from left to right in equal sections with small overlaps.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Inhibition Of Plc Via Pkamentioning

confidence: 99%

Section: The Interaction Between Pka and Phospholipase C (Plc)mentioning

confidence: 99%

Section: The Interaction Between Pka and Phospholipase C (Plc)mentioning

confidence: 99%

Section: Inhibition Of Plc Via Pkamentioning

confidence: 99%

See 3 more Smart Citations

Arginine vasopressin-induced glucagon release: interaction with glucose and cyclic AMP-dependent protein kinase

Abu-Basha

View full text Add to dashboard Cite

show abstract

Activated Protein Phosphatase 2A Disrupts Nutrient Sensing Balance Between Mechanistic Target of Rapamycin Complex 1 and Adenosine Monophosphate–Activated Protein Kinase, Causing Sarcopenia in Alcohol‐Associated Liver Disease

et al. 2021

View full text Add to dashboard Cite

BaCKgRoUND aND aIMS: Despite the high clinical significance of sarcopenia in alcohol-associated cirrhosis, there are currently no effective therapies because the underlying mechanisms are poorly understood. We determined the mechanisms of ethanol-induced impaired phosphorylation of mechanistic target of rapamycin complex 1 (mTORC1) and adenosine monophosphate-activated protein kinase (AMPK) with consequent dysregulated skeletal muscle protein homeostasis (balance between protein synthesis and breakdown). appRoaCH aND ReSUltS: Differentiated murine myotubes, gastrocnemius muscle from mice with loss and gain of function of regulatory genes following ethanol treatment, and skeletal muscle from patients with alcohol-associated cirrhosis were used. Ethanol increases skeletal muscle autophagy by dephosphorylating mTORC1, circumventing the classical kinase regulation by protein kinase B (Akt). Concurrently and paradoxically, ethanol exposure results in dephosphorylation and inhibition of AMPK, an activator of autophagy and inhibitor of mTORC1 signaling. However, AMPK remains inactive with ethanol exposure despite lower cellular and tissue adenosine triphosphate, indicating a "pseudofed" state. We identified protein phosphatase (PP) 2A as a key mediator of ethanol-induced signaling and functional perturbations using loss and gain of function studies. Ethanol impairs binding of endogenous inhibitor of PP2A to PP2A, resulting in methylation and targeting of PP2A to cause dephosphorylation of mTORC1 and AMPK. Activity of phosphoinositide 3-kinaseγ (PI3Kγ), a negative regulator of PP2A, was decreased in response to ethanol. Ethanol-induced molecular and phenotypic perturbations in wild-type mice were observed in PI3Kγ −/− mice even at baseline. Importantly, overexpressing kinase-active PI3Kγ but not the kinase-dead mutant reversed ethanol-induced molecular perturbations. CoNClUSIoNS:Our study describes the mechanistic underpinnings for ethanol-mediated dysregulation of protein homeostasis by PP2A that leads to sarcopenia with a potential for therapeutic approaches by targeting the PI3Kγ-PP2A axis.

show abstract

Mechanisms of Mallory Body Formation Induced by Okadaic Acid in Drug-Primed Mice

Yuan

Nagao

Gaal

et al. 1998

Experimental and Molecular Pathology

View full text Add to dashboard Cite

Interaction of Protein Phosphatases and Ethanol on Phospholipase C‐Mediated Intracellular Signal Transduction Processes in Rat Hepatocytes: Role of Protein Kinase A

Cited by 18 publications

References 17 publications

Arginine vasopressin-induced glucagon release: interaction with glucose and cyclic AMP-dependent protein kinase

Arginine vasopressin-induced glucagon release: interaction with glucose and cyclic AMP-dependent protein kinase

Activated Protein Phosphatase 2A Disrupts Nutrient Sensing Balance Between Mechanistic Target of Rapamycin Complex 1 and Adenosine Monophosphate–Activated Protein Kinase, Causing Sarcopenia in Alcohol‐Associated Liver Disease

Mechanisms of Mallory Body Formation Induced by Okadaic Acid in Drug-Primed Mice

Contact Info

Product

Resources

About