ER stress in pancreatic beta cells: the thin red line between adaptation and failure.

Abstract:

:Secretory cells, such as pancreatic beta cells, face the challenge of increasing protein synthesis severalfold during acute or chronic stimulation. This poses a burden on the endoplasmic reticulum (ER), the organelle where proinsulin synthesis and folding takes place. Thus, beta cells use various adaptive mechanisms to adjust the functional capacity of the ER to the prevailing demand. These check-and-balance mechanisms are collectively known as the unfolded protein response (UPR). It remains unclear how UPR signaling is ultimately regulated and what delineates the boundaries between a physiological and a pathological response. New discoveries point to the divergent effects of acute and chronic metabolic fluxes and chemical ER stressors on the formation of complexes among UPR transducers, scaffold proteins, and phosphatases. These and other findings provide a first glimpse on how different signals trigger diverging UPR outcomes.

journal_name

Sci Signal

journal_title

Science signaling

authors

Eizirik DL,Cnop M

doi

10.1126/scisignal.3110pe7

subject

Has Abstract

pub_date

2010-02-23 00:00:00

pages

pe7

issue

110

eissn

1945-0877

issn

1937-9145

pii

scisignal.3110pe7

journal_volume

3

pub_type

杂志文章,评审
  • Tumor suppression by PTEN requires the activation of the PKR-eIF2alpha phosphorylation pathway.

    abstract::Inhibition of protein synthesis by phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2) at Ser(51) occurs as a result of the activation of a family of kinases in response to various forms of stress. Although some consequences of eIF2alpha phosphorylation are cytoprotective, phospho...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2000389

    authors: Mounir Z,Krishnamoorthy JL,Robertson GP,Scheuner D,Kaufman RJ,Georgescu MM,Koromilas AE

    更新日期:2009-12-22 00:00:00

  • Target acquired: Selective autophagy in cardiometabolic disease.

    abstract::The accumulation of damaged or excess proteins and organelles is a defining feature of metabolic disease in nearly every tissue. Thus, a central challenge in maintaining metabolic homeostasis is the identification, sequestration, and degradation of these cellular components, including protein aggregates, mitochondria,...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.aag2298

    authors: Evans TD,Sergin I,Zhang X,Razani B

    更新日期:2017-02-28 00:00:00

  • Controlling the number of tooth rows.

    abstract::The organization and renewal capacity of teeth vary greatly among vertebrates. Mammals have only one row of teeth that are renewed at most once, whereas many nonmammalian species have multirowed dentitions and show remarkable capacity to replace their teeth throughout life. Although knowledge on the genetic basis of t...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.285pe53

    authors: Mikkola ML

    更新日期:2009-08-25 00:00:00

  • Real-time dynamics of peptide ligand-dependent receptor complex formation in planta.

    abstract::The CLAVATA (CLV) and flagellin (flg) signaling pathways act through peptide ligands and closely related plasma membrane-localized receptor-like kinases (RLKs). The plant peptide CLV3 regulates stem cell homeostasis, whereas the bacterial flg22 peptide elicits defense responses. We applied multiparameter fluorescence ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aab0598

    authors: Somssich M,Ma Q,Weidtkamp-Peters S,Stahl Y,Felekyan S,Bleckmann A,Seidel CA,Simon R

    更新日期:2015-08-04 00:00:00

  • Lack of the phosphatase PTPN22 increases adhesion of murine regulatory T cells to improve their immunosuppressive function.

    abstract::The cytoplasmic phosphatase PTPN22 (protein tyrosine phosphatase nonreceptor type 22) plays a key role in regulating lymphocyte homeostasis, which ensures that the total number of lymphocytes in the periphery remains relatively constant. Mutations in PTPN22 confer an increased risk of developing autoimmune diseases; h...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2003365

    authors: Brownlie RJ,Miosge LA,Vassilakos D,Svensson LM,Cope A,Zamoyska R

    更新日期:2012-11-27 00:00:00

  • Wingless promotes proliferative growth in a gradient-independent manner.

    abstract::Morphogens form concentration gradients that organize patterns of cells and control growth. It has been suggested that, rather than the intensity of morphogen signaling, it is its gradation that is the relevant modulator of cell proliferation. According to this view, the ability of morphogens to regulate growth during...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2000360

    authors: Baena-Lopez LA,Franch-Marro X,Vincent JP

    更新日期:2009-10-06 00:00:00

  • TACE activation by MAPK-mediated regulation of cell surface dimerization and TIMP3 association.

    abstract::Ectodomain shedding mediated by tumor necrosis factor-α (TNF-α)-converting enzyme [TACE; also known as ADAM17 (a disintegrin and metalloproteinase 17)] provides an important switch in regulating cell proliferation, inflammation, and cancer progression. TACE-mediated ectodomain cleavage is activated by signaling of the...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2002689

    authors: Xu P,Liu J,Sakaki-Yumoto M,Derynck R

    更新日期:2012-05-01 00:00:00

  • Lgl reduces endosomal vesicle acidification and Notch signaling by promoting the interaction between Vap33 and the V-ATPase complex.

    abstract::Epithelial cell polarity is linked to the control of tissue growth and tumorigenesis. The tumor suppressor and cell polarity protein lethal-2-giant larvae (Lgl) promotes Hippo signaling and inhibits Notch signaling to restrict tissue growth in Drosophila melanogaster Notch signaling is greater in lgl mutant tissue tha...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aar1976

    authors: Portela M,Yang L,Paul S,Li X,Veraksa A,Parsons LM,Richardson HE

    更新日期:2018-06-05 00:00:00

  • Differential p53-independent outcomes of p19(Arf) loss in oncogenesis.

    abstract::One reported function of the tumor suppressor p19(Arf) is to stabilize p53, providing a critical checkpoint in the response to oncogenic insults. Acute loss of Pten leads to an increase in the abundance of p19(Arf), p53, and p21 proteins as part of a fail-safe senescence response. Here, we report that loss of p19(Arf)...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2000053

    authors: Chen Z,Carracedo A,Lin HK,Koutcher JA,Behrendt N,Egia A,Alimonti A,Carver BS,Gerald W,Teruya-Feldstein J,Loda M,Pandolfi PP

    更新日期:2009-08-18 00:00:00

  • 4E-BP2 hardwires lymphocytes for rapamycin sensitivity.

    abstract::The mTORC1 [mammalian (or mechanistic) target of rapamycin complex 1] inhibitor rapamycin is a potent inhibitor of T and B lymphocyte growth and proliferation. In this issue of Science Signaling, So et al found that the isoform of 4E-BP (4E-BP2) in lymphocytes that regulates messenger RNA translation is more sensitive...

    journal_title:Science signaling

    pub_type: 评论,杂志文章,评审

    doi:10.1126/scisignal.aaf8190

    authors: Abraham RT

    更新日期:2016-05-31 00:00:00

  • De novo organ formation from differentiated cells: root nodule organogenesis.

    abstract::The symbiotic interaction between Rhizobium bacteria and legume plants leads to the induction of a new developmental program: the formation of nitrogen-fixing root nodules. Nodulation is triggered by specific bacterial signals, the Nod factors, and integrates plant developmental regulatory pathways to reactivate diffe...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.149re11

    authors: Crespi M,Frugier F

    更新日期:2008-12-09 00:00:00

  • Cycles of ubiquitination and deubiquitination critically regulate growth factor-mediated activation of Akt signaling.

    abstract::K63-linked ubiquitination of Akt is a posttranslational modification that plays a critical role in growth factor-mediated membrane recruitment and activation of Akt. Although E3 ligases involved in growth factor-induced ubiquitination of Akt have been defined, the deubiquitinating enzyme (DUB) that triggers deubiquiti...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2003197

    authors: Yang WL,Jin G,Li CF,Jeong YS,Moten A,Xu D,Feng Z,Chen W,Cai Z,Darnay B,Gu W,Lin HK

    更新日期:2013-01-08 00:00:00

  • TRPML1 channels initiate Ca2+ sparks in vascular smooth muscle cells.

    abstract::TRPML1 (transient receptor potential mucolipin 1) is a Ca2+-permeable, nonselective cation channel localized to the membranes of endosomes and lysosomes and is not present or functional on the plasma membrane. Ca2+ released from endosomes and lysosomes into the cytosol through TRPML1 channels is vital for trafficking,...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aba1015

    authors: Thakore P,Pritchard HAT,Griffin CS,Yamasaki E,Drumm BT,Lane C,Sanders KM,Feng Earley Y,Earley S

    更新日期:2020-06-23 00:00:00

  • Rounding up the usual suspects in O2 sensing: CO, NO, and H2S!

    abstract::Oxygen sensing by the carotid body is essential in vertebrates to adapt to reduced arterial oxygen tension. In this issue of Science Signaling, Yuan et al. report an intricate signaling system to transduce a physical parameter--oxygen tension--into a biological cellular signal (neural discharge) through changes in the...

    journal_title:Science signaling

    pub_type: 评论,杂志文章

    doi:10.1126/scisignal.aab1665

    authors: Fandrey J

    更新日期:2015-04-21 00:00:00

  • Nutrition-minded cell cycle.

    abstract::For decades, the fission yeast Schizosaccharomyces pombe has been used as an excellent model with which to explore how cellular growth is coordinated with the division cycle, a yet-unanswered question in biology. New studies in this organism show that TOR (target of rapamycin) kinase and stress-responsive MAPK (mitoge...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.296pe74

    authors: Shiozaki K

    更新日期:2009-11-10 00:00:00

  • MARK3-mediated phosphorylation of ARHGEF2 couples microtubules to the actin cytoskeleton to establish cell polarity.

    abstract::The PAR-1-MARK pathway controls cell polarity through the phosphorylation of microtubule-associated proteins. Rho-Rac guanine nucleotide exchange factor 2 (ARHGEF2), which activates Ras homolog family member A (RHOA), is anchored to the microtubule network and sequestered in an inhibited state through binding to dynei...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aan3286

    authors: Sandí MJ,Marshall CB,Balan M,Coyaud É,Zhou M,Monson DM,Ishiyama N,Chandrakumar AA,La Rose J,Couzens AL,Gingras AC,Raught B,Xu W,Ikura M,Morrison DK,Rottapel R

    更新日期:2017-10-31 00:00:00

  • Dynamic DNA methylation regulates neuronal intrinsic membrane excitability.

    abstract::Epigenetic modifications, such as DNA cytosine methylation, contribute to the mechanisms underlying learning and memory by coordinating adaptive gene expression and neuronal plasticity. Transcription-dependent plasticity regulated by DNA methylation includes synaptic plasticity and homeostatic synaptic scaling. Memory...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf5642

    authors: Meadows JP,Guzman-Karlsson MC,Phillips S,Brown JA,Strange SK,Sweatt JD,Hablitz JJ

    更新日期:2016-08-23 00:00:00

  • The chemokine CXCL12 generates costimulatory signals in T cells to enhance phosphorylation and clustering of the adaptor protein SLP-76.

    abstract::The CXC chemokine CXCL12 mediates the chemoattraction of T cells and enhances the stimulation of T cells through the T cell receptor (TCR). The adaptor SLP-76 [Src homology 2 (SH2) domain-containing leukocyte protein of 76 kD] has two key tyrosine residues, Tyr(113) and Tyr(128), that mediate signaling downstream of t...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2004018

    authors: Smith X,Schneider H,Köhler K,Liu H,Lu Y,Rudd CE

    更新日期:2013-07-30 00:00:00

  • AKAP150-dependent cooperative TRPV4 channel gating is central to endothelium-dependent vasodilation and is disrupted in hypertension.

    abstract::Endothelial cell dysfunction, characterized by a diminished response to endothelial cell-dependent vasodilators, is a hallmark of hypertension. TRPV4 channels play a major role in endothelial-dependent vasodilation, a function mediated by local Ca(2+) influx through clusters of functionally coupled TRPV4 channels rath...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2005052

    authors: Sonkusare SK,Dalsgaard T,Bonev AD,Hill-Eubanks DC,Kotlikoff MI,Scott JD,Santana LF,Nelson MT

    更新日期:2014-07-08 00:00:00

  • Aspirin ameliorates experimental autoimmune encephalomyelitis through interleukin-11-mediated protection of regulatory T cells.

    abstract::Multiple sclerosis (MS) is a human disease that results from autoimmune T cells targeting myelin protein that is expressed within the central nervous system. In MS, the number of FoxP3-expressing regulatory T cells (Tregs) is reduced, which facilitates the activation of autoreactive T cells. Because aspirin (acetylsal...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aar8278

    authors: Mondal S,Jana M,Dasarathi S,Roy A,Pahan K

    更新日期:2018-11-27 00:00:00

  • Arabidopsis jasmonate signaling pathway.

    abstract::Jasmonates control defense gene expression, growth, and fertility throughout the plant kingdom and have been studied extensively in Arabidopsis thaliana. The prohormone jasmonic acid (JA) is conjugated to amino acids such as isoleucine to form the active hormone jasmonoyl-isoleucine (JA-Ile). A series of breakthroughs...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.3109cm4

    authors: Gfeller A,Liechti R,Farmer EE

    更新日期:2010-02-16 00:00:00

  • Genetic diversity affects the nanoscale membrane organization and signaling of natural killer cell receptors.

    abstract::Genetic diversity in human natural killer (NK) cell receptors is linked to resistance and susceptibility to many diseases. Here, we tested the effect of this diversity on the nanoscale organization of killer cell immunoglobulin-like receptors (KIRs). Using superresolution microscopy, we found that inhibitory KIRs enco...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaw9252

    authors: Kennedy PR,Barthen C,Williamson DJ,Pitkeathly WTE,Hazime KS,Cumming J,Stacey KB,Hilton HG,Carrington M,Parham P,Davis DM

    更新日期:2019-12-17 00:00:00

  • Nucleolar localization of a netrin-1 isoform enhances tumor cell proliferation.

    abstract::Netrin-1 displays proto-oncogenic activity in several cancers, which is thought to be due to the ability of this secreted cue to stimulate survival when bound to its receptors. We showed that in contrast to full-length, secreted netrin-1, some cancer cells produced a truncated intranuclear form of netrin-1 (ΔN-netrin-...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2002456

    authors: Delloye-Bourgeois C,Goldschneider D,Paradisi A,Therizols G,Belin S,Hacot S,Rosa-Calatrava M,Scoazec JY,Diaz JJ,Bernet A,Mehlen P

    更新日期:2012-08-07 00:00:00

  • Evolution of human, chicken, alligator, frog, and zebrafish mineralocorticoid receptors: Allosteric influence on steroid specificity.

    abstract::Although multiple steroid ligands of the glucocorticoid, mineralocorticoid, and progestin families bind to and regulate the activity of mineralocorticoid receptors (MRs), the responses to these ligands differ across species. To understand how the different domains of MRs contribute to the ligand-induced activation or ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aao1520

    authors: Katsu Y,Oka K,Baker ME

    更新日期:2018-07-03 00:00:00

  • Bacterial invaders drive CRC progression.

    abstract::The oral bacterium Fusobacterium nucleatum is often found in colorectal cancer (CRC). In the 21 July 2020 issue of Science Signaling, Casasanta et al show that CRC cell-resident F. nucleatum promotes cytokine secretion that may potentiate tumor growth and metastatic progression in patients. ...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.abc4218

    authors: Meyerson M

    更新日期:2020-08-11 00:00:00

  • Itk controls the spatiotemporal organization of T cell activation.

    abstract::During T cell activation by antigen-presenting cells (APCs), the diverse spatiotemporal organization of components of T cell signaling pathways modulates the efficiency of activation. Here, we found that loss of the tyrosine kinase interleukin-2 (IL-2)-inducible T cell kinase (Itk) in mice altered the spatiotemporal d...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2001821

    authors: Singleton KL,Gosh M,Dandekar RD,Au-Yeung BB,Ksionda O,Tybulewicz VL,Altman A,Fowell DJ,Wülfing C

    更新日期:2011-10-04 00:00:00

  • The cytoplasmic tail of MUC1: a very busy place.

    abstract::The role of mucin 1 (MUC1) in protecting epithelia from microbial infection, enzymatic digestion, and other irritants has been appreciated for some time. In addition, MUC1 serves as a barrier to embryo implantation. MUC1 is highly abundant in many tumors in which its role in barrier function may serve to protect cells...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.127pe35

    authors: Carson DD

    更新日期:2008-07-08 00:00:00

  • TGF-β receptor I/II trafficking and signaling at primary cilia are inhibited by ceramide to attenuate cell migration and tumor metastasis.

    abstract::Signaling by the transforming growth factor-β (TGF-β) receptors I and II (TβRI/II) and the primary cilia-localized sonic hedgehog (Shh) pathway promote cell migration and, consequently, tumor metastasis. In contrast, the sphingolipid ceramide inhibits cell proliferation and tumor metastasis. We investigated whether ce...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aam7464

    authors: Gencer S,Oleinik N,Kim J,Panneer Selvam S,De Palma R,Dany M,Nganga R,Thomas RJ,Senkal CE,Howe PH,Ogretmen B

    更新日期:2017-10-24 00:00:00

  • STIM2 enhances receptor-stimulated Ca²⁺ signaling by promoting recruitment of STIM1 to the endoplasmic reticulum-plasma membrane junctions.

    abstract::A central component of receptor-evoked Ca(2+) signaling is store-operated Ca(2+) entry (SOCE), which is activated by the assembly of STIM1-Orai1 channels in endoplasmic reticulum (ER) and plasma membrane (PM) (ER-PM) junctions in response to depletion of ER Ca(2+). We report that STIM2 enhances agonist-mediated activa...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2005748

    authors: Ong HL,de Souza LB,Zheng C,Cheng KT,Liu X,Goldsmith CM,Feske S,Ambudkar IS

    更新日期:2015-01-13 00:00:00

  • LRP6 mediates cAMP generation by G protein-coupled receptors through regulating the membrane targeting of Gα(s).

    abstract::Ligand binding to certain heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) stimulates the rapid synthesis of cyclic adenosine monophosphate (cAMP) through the G protein α(s) subunit, which activates adenylyl cyclase (AC). We found that the transmembrane receptor low-density lipop...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2001464

    authors: Wan M,Li J,Herbst K,Zhang J,Yu B,Wu X,Qiu T,Lei W,Lindvall C,Williams BO,Ma H,Zhang F,Cao X

    更新日期:2011-03-15 00:00:00