scholarly journals Phosphorylation of SNX27 by MAPK11/14 links cellular stress–signaling pathways with endocytic recycling

2021 ◽  
Vol 220 (4) ◽  
Author(s):  
Lejiao Mao ◽  
Chenyi Liao ◽  
Jiao Qin ◽  
Yanqiu Gong ◽  
Yifei Zhou ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cellular Stress ◽  
Binding Pocket ◽  
Stress Signaling ◽  
Lysosomal Degradation ◽  
Endocytic Recycling ◽  
Cargo Proteins ◽  
Extracellular Stimuli ◽  
Save Energy ◽  
Golgi Network

Endocytosed proteins can be delivered to lysosomes for degradation or recycled to either the trans-Golgi network or the plasma membrane. It remains poorly understood how the recycling versus degradation of cargoes is determined. Here, we show that multiple extracellular stimuli, including starvation, LPS, IL-6, and EGF treatment, can strongly inhibit endocytic recycling of multiple cargoes through the activation of MAPK11/14. The stress-induced kinases in turn directly phosphorylate SNX27, a key regulator of endocytic recycling, at serine 51 (Ser51). Phosphorylation of SNX27 at Ser51 alters the conformation of its cargo-binding pocket and decreases the interaction between SNX27 and cargo proteins, thereby inhibiting endocytic recycling. Our study indicates that endocytic recycling is highly dynamic and can crosstalk with cellular stress–signaling pathways. Suppression of endocytic recycling and enhancement of receptor lysosomal degradation serve as new mechanisms for cells to cope with stress and save energy.

Stress sensing within the breast tumor microenvironment: how glucocorticoid receptors live in the moment

2021 ◽  
Author(s):  
Carlos Perez Kerkvliet ◽  
Thu H. Truong ◽  
Julie Hanson Ostrander ◽  
Carol A. Lange
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Signaling Pathways ◽  
Cancer Biology ◽  
Transcriptional Activity ◽  
Cellular Stress ◽  
Mapk Signaling ◽  
Cellular Growth ◽  
Steroid Hormone Receptors ◽  
Stress Signaling

Abstract The classification and treatment of breast cancer is largely defined by the expression of steroid hormone receptors (HRs), namely estrogen receptor (ER) and progesterone receptor (PR), and gene amplification/overexpression of human epidermal growth factor receptor 2 (HER2). More recently, studies of androgen receptor (AR), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR) have revealed that targeting these related HRs may be a promising strategy for a more personalized approach to the treatment of specific subtypes of HR+ breast cancer. For example, GR expression is associated with a good prognosis in ER+ breast cancer, but predicts poor prognosis in triple-negative breast cancer (TNBC). GR, like ER, PRs, and AR, is a ligand-activated transcription factor, but also has significant ligand-independent signaling activities. GR transcriptional activity is classically regulated by circulating glucocorticoids (GCs; ligand-dependent). Recent studies demonstrate that GR transcriptional activity is also regulated by a variety of cellular stress stimuli that input to GR Ser134 phosphorylation via rapid activation of the p38 mitogen activated protein kinase (MAPK) signaling pathway (ligand-independent). Furthermore, ligand-independent GR activation promotes feedforward signaling loops that mediate sustained activation of stress signaling pathways to drive advanced cancer biology (i.e. migration, invasion, chemoresistance, survival, and cellular growth). In this review, we will focus on the role of GR as a key sensor and mediator of physiologic and tumor microenvironment (TME)-derived cellular stress signaling in TNBC and discuss how targeting GR and/or associated signaling pathways may provide a strategy to inhibit deadly TNBC progression.

Calcium sensors and their stress signaling pathways in plants

2013 ◽  
Vol 35 (7) ◽  
pp. 875-884 ◽  
Author(s):  
Zhong-Zhong ZHENG ◽  
Jin-Qiu SHEN ◽  
Wei-Huai PAN ◽  
Jian-Wei PAN
Keyword(s):  
Signaling Pathways ◽  
Stress Signaling ◽  
Calcium Sensors

scholarly journals Enrichment of Acyl Coenzyme A:CholesterolO-Acyltransferase NearTrans-Golgi Network and Endocytic Recycling Compartment

2000 ◽  
Vol 20 (7) ◽  
pp. 1769-1776 ◽  
Author(s):  
Nadia Khelef ◽  
T. T. Soe ◽  
Oswald Quehenberger ◽  
Nanda Beatini ◽  
Ira Tabas ◽  
...  
Keyword(s):  
Endocytic Recycling ◽  
Golgi Network

159 In vitro Characterization of Potential Pig Calcium-sensing Receptor (CaSR) Ligands and Cell Signaling Pathways Related to CaSR Activation by a Dual-luciferase Reporter Assay

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 82-83
Author(s):  
Xiaoya Zhao ◽  
Qianru Hui ◽  
Paula Azevedo ◽  
Karmin O ◽  
Chengbo Yang
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Binding Pocket ◽  
Extracellular Calcium ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Biased Agonism ◽  
Calcium Sensing ◽  
Dual Luciferase Reporter Assay

Abstract The calcium-sensing receptor (CaSR) is a pivotal regulator of calcium homeostasis. Our previous study has found that pig CaSR (pCaSR) is widely expressed in intestinal segments in weaned piglets. To characterize the activation of pCaSR by potential ligands and related cell signaling pathways, a dual-luciferase reporter assay was employed for the ligands screening and molecular docking was utilized to predict the binding mode of identified ligands. Our results showed that the dual-luciferase reporter assay system was well suited for pCaSR research and its ligand screening. The extracellular calcium activated pCaSR in a concentration-dependent manner with a half-maximal effective concentration (EC50) = 4.74 mM through the Gq/11 signaling pathway, EC50 = 2.85 mM through extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation signaling pathway, and EC50 = 2.26 mM through the Ras homolog family member A (RhoA) activation signaling pathway. Moreover, the activation of pCaSR stimulated by extracellular calcium showed biased agonism through three main signaling pathways: ERK1/2 phosphorylation signaling, Gq/11 signaling, and G12/13 signaling. Both L-Tryptophan and α-casein (90–95) could activate the pCaSR in the presence of extracellular calcium. Furthermore, we characterized the L-tryptophan binding pocket formed by pCaSR residues TRP 70, SER 147, ALA168, SER 169, SER 170, ASP 190, GLU 297, ALA 298, and ILE 416, as well as the α-casein (90–95) binding pocket formed by pCaSR residues PRO188, ASN189, GLU191, HIS192, LYS225, LEU242, ASP480, VAL486, GLY487, VAL513, and TYR514. In conclusion, similar to the human CaSR, the pCaSR also shows biased agonism through three main signaling pathways and both α-casein (90–95) and L-tryptophan are agonists for pCaSR. Furthermore, the binding sites of α-casein (90–95) and L-tryptophan are mainly located within the extracellular domain of pCaSR.

Lifetime bioaccumulation of silver nanoparticles accelerates functional aging by inactivating antioxidant pathways, an effect reversed by pterostilbene

2021 ◽  
Author(s):  
Zi-Yu Chen ◽  
Yu-Chen Su ◽  
Fong-Yu Cheng ◽  
Shian-Jang Yan ◽  
Ying-Jan Wang
Keyword(s):  
Reactive Oxygen Species ◽  
Silver Nanoparticles ◽  
Adverse Effects ◽  
Signaling Pathways ◽  
Reactive Oxygen ◽  
Engineered Nanoparticles ◽  
Stress Signaling ◽  
Oxygen Species ◽  
Safety Concerns

Engineered nanoparticles raise safety concerns. Silver nanoparticles (AgNPs) exert acute and chronic adverse effects by inducing reactive oxygen species (ROS)-mediated stress signaling pathways. We investigated the mechanisms by which AgNPs...

Lycopene Ameliorates Atrazine-Induced Pyroptosis in Spleen via Suppressing the Ox-mtDNA/Nlrp3 Inflammasome Pathway

2021 ◽  
Author(s):  
Shi-Yong Zhu ◽  
Jian-Ying Guo ◽  
Jin-Yang Li ◽  
Xueyan Dai ◽  
Xue-Nan Li ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Cellular Stress ◽  
Integration Point ◽  
Extracellular Stimuli

Nlrp3 is a vital integration point of diverse extracellular stimuli and cellular stress. However, inappropriate activation of Nlrp3 results in progression of autoinflammatory and metabolic disorders. Atrazine, using widely in...

Cell Stress Signaling Cascades Regulating Cell Fate

2018 ◽  
Vol 24 (27) ◽  
pp. 3176-3183 ◽  
Author(s):  
Rohit Gundamaraju ◽  
Ravichandra Vemuri ◽  
Wai Chin Chong ◽  
Dominic P. Geraghty ◽  
Rajaraman Eri
Keyword(s):  
Cell Death ◽  
Cell Fate ◽  
Stress Responses ◽  
Cellular Stress ◽  
Cell Stress ◽  
Signaling Cascades ◽  
Stress Signaling ◽  
Cell Type ◽  
Induce Cell Death ◽  
Stressed Cell

Initiating anti-apoptotic signaling or triggering cell death depends to a great extent on the nature or source of cellular stress and cell type. Interplay between each stress response eventually determines the fate of stressed cell. Numerous factors induce cell death by a number of pathways including apoptosis, autophagy and necrosis. Not surprisingly, some of the pathways are interrelated to each other through a mediator that could articulate the entire mechanism. The present review attempts to consolidate all the pathways included in intrinsic cellular stress such as oxidative stress and autophagy, endoplasmic reticular stress (ERS) and mitophagy and apoptosis as fate in cell stress. These stress responses are a hallmark of numerous diseases including neurodegenerative diseases, diabetes and cancer. Understanding the cross-talk between different intrinsic cell stress responses will help to develop new therapeutic targets and hence lead to the development of new therapeutics.

scholarly journals Senescent Growth Arrest in Mesenchymal Stem Cells Is Bypassed by Wip1-Mediated Downregulation of Intrinsic Stress Signaling Pathways

Stem Cells ◽  
2009 ◽  
Vol 27 (8) ◽  
pp. 1963-1975 ◽  
Author(s):  
Ji-Seon Lee ◽  
Mi-Ok Lee ◽  
Bo-Hyun Moon ◽  
Sung Han Shim ◽  
Albert J. Fornace ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Growth Arrest ◽  
Intrinsic Stress ◽  
Stress Signaling
Sign in / Sign up

Export Citation Format

Share Document