Scaffolding of Mitogen-Activated Protein Kinase Signaling by β-Arrestins

Kim, Kiae; Han, Yeonjin; Duan, Longhan; Chung, Ka Young

doi:10.3390/ijms23021000

Cited by 12 publications

(12 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In another scaffolding role, β-arrestin can assemble the entire extracellular signal-regulated kinase (ERK/MAPK [mitogenactivated protein kinase]) cascade. It has binding sites for sequentially acting cRaf (MAPK kinase kinase), MEK (MAPK kinase), and ERK (MAPK) that mediate a signaling cascade for cell proliferation, cell migration, and actin dynamics after activation of G-protein coupled receptors (Luttrell et al, 2001;Shenoy and Lefkowitz, 2011;Jung et al, 2017;Kim et al, 2022). In our work with optical probes and single-molecule total internal reflection fluorescence, we saw a recruitment and loose (reversible in seconds) association of β-arrestin with M 1 receptors developing in ∼5 s (half time) of agonist application, followed by a stable (reversible only in many minutes) receptor association with β-arrestin developing in 10 min, and phosphorylation of ERK accumulating slowly over 5-10 min (Jung et al, 2017;Jung and Hille, 2019).…”

Section: Examples Of Metabolic Controlmentioning

confidence: 99%

Biophysical physiology of phosphoinositide rapid dynamics and regulation in living cells

Jensen

Falkenburger

Dickson

et al. 2022

Journal of General Physiology

View full text Add to dashboard Cite

Phosphoinositide membrane lipids are ubiquitous low-abundance signaling molecules. They direct many physiological processes that involve ion channels, membrane identification, fusion of membrane vesicles, and vesicular endocytosis. Pools of these lipids are continually broken down and refilled in living cells, and the rates of some of these reactions are strongly accelerated by physiological stimuli. Recent biophysical experiments described here measure and model the kinetics and regulation of these lipid signals in intact cells. Rapid on-line monitoring of phosphoinositide metabolism is made possible by optical tools and electrophysiology. The experiments reviewed here reveal that as for other cellular second messengers, the dynamic turnover and lifetimes of membrane phosphoinositides are measured in seconds, controlling and timing rapid physiological responses, and the signaling is under strong metabolic regulation. The underlying mechanisms of this metabolic regulation remain questions for the future.

show abstract

Section: Examples Of Metabolic Controlmentioning

confidence: 99%

Biophysical physiology of phosphoinositide rapid dynamics and regulation in living cells

Jensen

Falkenburger

Dickson

et al. 2022

Journal of General Physiology

View full text Add to dashboard Cite

show abstract

“…Meanwhile, β-arrestins also interact with the intracellular signaling proteins ( 47 ). Mitogen-activated protein kinases (MAPK) cascade is an important signaling pathway for β-arrestin-activated intracellular signaling molecules ( 48 ).…”

Section: Ffa Receptorsmentioning

confidence: 99%

Free fatty acid receptors in the endocrine regulation of glucose metabolism: Insight from gastrointestinal-pancreatic-adipose interactions

Zhao

2022

Front. Endocrinol.

View full text Add to dashboard Cite

Glucose metabolism is primarily controlled by pancreatic hormones, with the coordinated assistance of the hormones from gastrointestine and adipose tissue. Studies have unfolded a sophisticated hormonal gastrointestinal-pancreatic-adipose interaction network, which essentially maintains glucose homeostasis in response to the changes in substrates and nutrients. Free fatty acids (FFAs) are the important substrates that are involved in glucose metabolism. FFAs are able to activate the G-protein coupled membrane receptors including GPR40, GPR120, GPR41 and GPR43, which are specifically expressed in pancreatic islet cells, enteroendocrine cells as well as adipocytes. The activation of FFA receptors regulates the secretion of hormones from pancreas, gastrointestine and adipose tissue to influence glucose metabolism. This review presents the effects of the FFA receptors on glucose metabolism via the hormonal gastrointestinal-pancreatic-adipose interactions and the underlying intracellular mechanisms. Furthermore, the development of therapeutic drugs targeting FFA receptors for the treatment of abnormal glucose metabolism such as type 2 diabetes mellitus is summarized.

show abstract

“…More recent evidence suggests that some internalized GPCR/ β-arrestin complexes result in sustained activation of adenylylcyclase and/or β-arrestin dependent activation of Src, extracellular signal regulated kinase (ERK1/2), c-Jun-Nterminal kinase (JNK), and p38 MAPK (Shenoy et al, 2006;Pakharukova et al, 2020;Kim et al, 2022). The extent of GRKmediated phosphorylation determines the stability of GPCR/βarrestin complexes.…”

Section: Relevance Of β-Arrestins As Negative and Positive Regulators...mentioning

confidence: 99%

Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling

Zhou

Torres

2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

Autosomal dominant polycystic kidney disease (ADPKD), with an estimated genetic prevalence between 1:400 and 1:1,000 individuals, is the third most common cause of end stage kidney disease after diabetes mellitus and hypertension. Over the last 3 decades there has been great progress in understanding its pathogenesis. This allows the stratification of therapeutic targets into four levels, gene mutation and polycystin disruption, proximal mechanisms directly caused by disruption of polycystin function, downstream regulatory and signaling pathways, and non-specific pathophysiologic processes shared by many other diseases. Dysfunction of the polycystins, encoded by the PKD genes, is closely associated with disruption of calcium and upregulation of cyclic AMP and protein kinase A (PKA) signaling, affecting most downstream regulatory, signaling, and pathophysiologic pathways altered in this disease. Interventions acting on G protein coupled receptors to inhibit of 3′,5′-cyclic adenosine monophosphate (cAMP) production have been effective in preclinical trials and have led to the first approved treatment for ADPKD. However, completely blocking cAMP mediated PKA activation is not feasible and PKA activation independently from cAMP can also occur in ADPKD. Therefore, targeting the cAMP/PKA/CREB pathway beyond cAMP production makes sense. Redundancy of mechanisms, numerous positive and negative feedback loops, and possibly counteracting effects may limit the effectiveness of targeting downstream pathways. Nevertheless, interventions targeting important regulatory, signaling and pathophysiologic pathways downstream from cAMP/PKA activation may provide additive or synergistic value and build on a strategy that has already had success. The purpose of this manuscript is to review the role of cAMP and PKA signaling and their multiple downstream pathways as potential targets for emergent therapies for ADPKD.

show abstract

Scaffolding of Mitogen-Activated Protein Kinase Signaling by β-Arrestins

Cited by 12 publications

References 81 publications

Biophysical physiology of phosphoinositide rapid dynamics and regulation in living cells

Biophysical physiology of phosphoinositide rapid dynamics and regulation in living cells

Free fatty acid receptors in the endocrine regulation of glucose metabolism: Insight from gastrointestinal-pancreatic-adipose interactions

Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling

Contact Info

Product

Resources

About