Abstract 973: Coordinated regulation of cap-dependent translation and microRNA function by convergent signaling through the PI3K/Akt/mTOR and Jak/Stat/Pim signaling pathways

2015 ◽  
Author(s):  
Scott H. Olejniczak ◽  
Gaspare La Rocca ◽  
Megan Radler ◽  
Craig B. Thompson
Keyword(s):  
Signaling Pathways ◽  
Coordinated Regulation ◽  
Microrna Function

Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways

2014 ◽  
Vol 26 (2) ◽  
pp. 192-197 ◽  
Author(s):  
Dexi Zhou ◽  
Cheng Huang ◽  
Zhen Lin ◽  
Shuxiang Zhan ◽  
Lingna Kong ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cellular Signaling ◽  
Macrophage Polarization ◽  
Coordinated Regulation ◽  
And Function

scholarly journals Coordinated Regulation of Cap-Dependent Translation and MicroRNA Function by Convergent Signaling Pathways

2016 ◽  
Vol 36 (18) ◽  
pp. 2360-2373 ◽  
Author(s):  
Scott H. Olejniczak ◽  
Gaspare La Rocca ◽  
Megan R. Radler ◽  
Shawn M. Egan ◽  
Qing Xiang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Immune Cells ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Cellular Activation ◽  
Cellular Processes ◽  
Eukaryotic Initiation Factor 4E ◽  
Pim Kinases ◽  
Cell Growth And Proliferation ◽  
Microrna Function

Cell growth and proliferation require the coordinated activation of many cellular processes, including cap-dependent mRNA translation. MicroRNAs oppose cap-dependent translation and set thresholds for expression of target proteins. Emerging data suggest that microRNA function is enhanced by cellular activation due in part to induction of the RNA-induced silencing complex (RISC) scaffold protein GW182. In the current study, we demonstrate that increased expression of GW182 in activated or transformed immune cells results from effects of phosphoinositol 3-kinase–Akt–mechanistic target of rapamycin (PI3K-Akt-mTOR) and Jak-Stat-Pim signaling on the translation of GW182 mRNA. Both signaling pathways enhanced polysome occupancy and eukaryotic initiation factor 4E (eIF4E) binding to the 5′ 7mG cap of GW182 mRNA. The effect of Jak-Stat-Pim signaling on polysome occupancy and expression of GW182 protein was greater than that of PI3K-Akt-mTOR signaling, likely resulting from enhanced eIF4A-dependent unwinding of G-quadruplexes in the 5′ untranslated region of GW182 mRNA. Consistent with this, GW182 expression and microRNA function were reduced by inhibition of mTOR or Pim kinases, translation initiation complex assembly, or eIF4A function. Taken together, these data provide a mechanistic link between microRNA function and cap-dependent translation that allows activated immune cells to maintain microRNA-mediated repression of targets despite enhanced rates of protein synthesis.

A compendium of G-protein–coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure

2020 ◽  
Vol 134 (5) ◽  
pp. 473-512 ◽  
Author(s):  
Ryan P. Ceddia ◽  
Sheila Collins
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Signaling Pathways ◽  
G Protein ◽  
Uncoupling Protein ◽  
Beige Adipocytes ◽  
Nucleotide Regulation ◽  
Ucp1 Expression ◽  
Thermogenic Adipocytes ◽  
G Protein Coupled

Abstract With the ever-increasing burden of obesity and Type 2 diabetes, it is generally acknowledged that there remains a need for developing new therapeutics. One potential mechanism to combat obesity is to raise energy expenditure via increasing the amount of uncoupled respiration from the mitochondria-rich brown and beige adipocytes. With the recent appreciation of thermogenic adipocytes in humans, much effort is being made to elucidate the signaling pathways that regulate the browning of adipose tissue. In this review, we focus on the ligand–receptor signaling pathways that influence the cyclic nucleotides, cAMP and cGMP, in adipocytes. We chose to focus on G-protein–coupled receptor (GPCR), guanylyl cyclase and phosphodiesterase regulation of adipocytes because they are the targets of a large proportion of all currently available therapeutics. Furthermore, there is a large overlap in their signaling pathways, as signaling events that raise cAMP or cGMP generally increase adipocyte lipolysis and cause changes that are commonly referred to as browning: increasing mitochondrial biogenesis, uncoupling protein 1 (UCP1) expression and respiration.

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