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

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

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

更新日期：2012-05-01 00:00:00

abstract：:The trimeric intracellular cation (TRIC) channels TRIC-A and TRIC-B localize predominantly to the endoplasmic reticulum (ER) and likely support Ca(2+) release from intracellular stores by mediating cationic flux to maintain electrical neutrality. Deletion and point mutations in TRIC-B occur in families with autosomal ...

journal_title：Science signaling

authors： Zhao C,Ichimura A,Qian N,Iida T,Yamazaki D,Noma N,Asagiri M,Yamamoto K,Komazaki S,Sato C,Aoyama F,Sawaguchi A,Kakizawa S,Nishi M,Takeshima H

更新日期：2016-05-17 00:00:00

abstract：:Genetically encoded fluorescent sensors enable cell-specific measurements of ions and small molecules in real time. Cyclic adenosine monophosphate (cAMP) is one of the most important signaling molecules in virtually all cell types and organisms. We describe cAMPr, a new single-wavelength cAMP sensor. We developed cAMP...

journal_title：Science signaling

authors： Hackley CR,Mazzoni EO,Blau J

更新日期：2018-03-06 00:00:00

abstract：:Prokaryotic cell wall biosynthesis is coordinated with cell growth and division, but the mechanisms regulating this dynamic process remain obscure. Here, we describe a phosphorylation-dependent regulatory complex that controls peptidoglycan (PG) biosynthesis in Mycobacterium tuberculosis. We found that PknB, a PG-resp...

journal_title：Science signaling

authors： Gee CL,Papavinasasundaram KG,Blair SR,Baer CE,Falick AM,King DS,Griffin JE,Venghatakrishnan H,Zukauskas A,Wei JR,Dhiman RK,Crick DC,Rubin EJ,Sassetti CM,Alber T

更新日期：2012-01-24 00:00:00

abstract：:Notch signaling is used to choose cell fates in many developmental contexts. New evidence shows that circulating blood cells in Drosophila, in the absence of Notch ligand provided by neighboring cells, activate Notch signaling through stabilization with the hypoxia-inducible factor-α (HIF-α) transcription factor. Alth...

journal_title：Science signaling

authors： Johnson EA

更新日期：2011-07-12 00:00:00

abstract：:Deoxyhypusine synthase (DHPS) uses the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly defined mechanisms. Because germline deletion of Dhps is embryonically lethal, its role in normal postnatal cellular function in vivo remains un...

journal_title：Science signaling

authors： Levasseur EM,Yamada K,Piñeros AR,Wu W,Syed F,Orr KS,Anderson-Baucum E,Mastracci TL,Maier B,Mosley AL,Liu Y,Bernal-Mizrachi E,Alonso LC,Scott D,Garcia-Ocaña A,Tersey SA,Mirmira RG

更新日期：2019-12-03 00:00:00

abstract：:Chemokines were initially thought of only as regulators of the migration of developing thymocytes between different compartments of the thymus and were predicted also to be involved in early stages of thymocyte development. Recent data have suggested additional functions for the chemokine receptor CXCR4-a G protein-co...

journal_title：Science signaling

authors： Ahamed JA,Madhivadhani P

更新日期：2010-04-27 00:00:00

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

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

abstract：:Mechanical loading of the skeleton is essential for the development, growth, and maintenance of strong, weight-bearing bones. Bone strength is plastic and can be modulated in adults, as illustrated by the increased bone mass in the playing arms of athletes as compared with their nonplaying arms. Our studies have shown...

journal_title：Science signaling

authors： Turner CH,Warden SJ,Bellido T,Plotkin LI,Kumar N,Jasiuk I,Danzig J,Robling AG

更新日期：2009-04-28 00:00:00

abstract：:Vitamin E is a fat-soluble vitamin with antioxidant properties. Tocopherols are the predominant form of vitamin E found in the diet and in supplements and have garnered interest for their potential cancer therapeutic and preventive effects, such as the dephosphorylation of Akt, a serine/threonine kinase with a pivotal...

journal_title：Science signaling

authors： Huang PH,Chuang HC,Chou CC,Wang H,Lee SL,Yang HC,Chiu HC,Kapuriya N,Wang D,Kulp SK,Chen CS

更新日期：2013-03-19 00:00:00

abstract：:The prefibrillar form of soluble amyloid-β (sAβ1-42) impairs synaptic function and is associated with the early phase of Alzheimer's disease (AD). We investigated how sAβ1-42 led to presynaptic defects using a quantum dot-based, single particle-tracking method to monitor synaptic vesicle (SV) trafficking along axons. ...

journal_title：Science signaling

authors： Park D,Na M,Kim JA,Lee U,Cho E,Jang M,Chang S

更新日期：2017-07-11 00:00:00

abstract：:Phosphoinositide 3-kinases (PI3Ks) are implicated in a broad spectrum of cellular activities, such as growth, proliferation, differentiation, migration, and metabolism. Activation of class I PI3Ks by mutation or overexpression correlates with the development and maintenance of various human cancers. These PI3Ks are he...

journal_title：Science signaling

authors： Vadas O,Burke JE,Zhang X,Berndt A,Williams RL

更新日期：2011-10-18 00:00:00

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

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

abstract：:Double knockout of PTEN and LKB1-genes encoding phosphatase and tensin homolog and liver kinase B1, respectively-leads to the spontaneous development of cancer in mice. PTEN converts phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to phosphatidylinositol (4,5)-bisphosphate (PIP2), whereas LKB1 activates the 5' adeno...

journal_title：Science signaling

authors： Chen J,Zhang XD,Proud C

更新日期：2015-09-01 00:00:00

abstract：:The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteo...

journal_title：Science signaling

authors： Gao J,Aksoy BA,Dogrusoz U,Dresdner G,Gross B,Sumer SO,Sun Y,Jacobsen A,Sinha R,Larsson E,Cerami E,Sander C,Schultz N

更新日期：2013-04-02 00:00:00

abstract：:Dimers of conventional transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) ligands are composed of two 100- to 140-amino acid peptides that are produced through the proteolytic processing of a proprotein precursor by proconvertases, such as furin. We report the identification of an evolutionarily...

journal_title：Science signaling

authors： Akiyama T,Marqués G,Wharton KA

更新日期：2012-04-03 00:00:00

abstract：:Degrons are the elements that are used by E3 ubiquitin ligases to target proteins for degradation. Most degrons are short linear motifs embedded within the sequences of modular proteins. As regulatory sites for protein abundance, they are important for many different cellular processes, such as progression through the...

journal_title：Science signaling

authors： Mészáros B,Kumar M,Gibson TJ,Uyar B,Dosztányi Z

更新日期：2017-03-14 00:00:00

abstract：:In a mouse model of Parkinson's disease, new evidence shows that l-DOPA, which is used to treat the symptoms of the disease but also causes dyskinesia, results in a persistent activation of the protein kinase mTOR (mammalian target of rapamycin) in a subset of striatal medium spiny neurons. Moreover, blockade of a spe...

journal_title：Science signaling

authors： Klann E

更新日期：2009-07-21 00:00:00

abstract：:Activation of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) by VEGF binding is critical for vascular morphogenesis. In addition, VEGF disrupts the endothelial barrier by triggering the phosphorylation and turnover of the junctional molecule VE-cadherin, a process mediated by the VEGFR2 downstream effec...

journal_title：Science signaling

authors： Gordon EJ,Fukuhara D,Weström S,Padhan N,Sjöström EO,van Meeteren L,He L,Orsenigo F,Dejana E,Bentley K,Spurkland A,Claesson-Welsh L

更新日期：2016-07-19 00:00:00

abstract：:A challenge for biomedical research is the development of pharmaceuticals that appropriately target disease mechanisms. Natural products can be a rich source of bioactive chemicals for medicinal applications but can act through unknown mechanisms and can be difficult to produce or obtain. To address these challenges, ...

journal_title：Science signaling

authors： Potts MB,Kim HS,Fisher KW,Hu Y,Carrasco YP,Bulut GB,Ou YH,Herrera-Herrera ML,Cubillos F,Mendiratta S,Xiao G,Hofree M,Ideker T,Xie Y,Huang LJ,Lewis RE,MacMillan JB,White MA

更新日期：2013-10-15 00:00:00

abstract：:The C-terminal guanine nucleotide exchange factor (GEF) module of Trio (TrioC) transfers signals from the Gαq/11 subfamily of heterotrimeric G proteins to the small guanosine triphosphatase (GTPase) RhoA, enabling Gαq/11-coupled G protein-coupled receptors (GPCRs) to control downstream events, such as cell motility an...

journal_title：Science signaling

authors： Bandekar SJ,Arang N,Tully ES,Tang BA,Barton BL,Li S,Gutkind JS,Tesmer JJG

更新日期：2019-02-19 00:00:00

abstract：:Educated natural killer (NK) cells have inhibitory receptors specific for self major histocompatibility complex (MHC) class I molecules and kill cancer cells more efficiently than do NK cells that do not have such receptors (hyporesponsive NK cells). The mechanism behind this functional empowerment through education h...

journal_title：Science signaling

authors： Staaf E,Hedde PN,Bagawath Singh S,Piguet J,Gratton E,Johansson S

更新日期：2018-02-13 00:00:00

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

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

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

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

更新日期：2017-02-28 00:00:00

abstract：:The cytokines of the transforming growth factor-β (TGF-β) family promote the growth and differentiation of multiple tissues, but the role of only the founding member, TGF-β, in regulating the immune responses has been extensively studied. TGF-β is critical to prevent the spontaneous activation of self-reactive T cells...

journal_title：Science signaling

authors： Browning LM,Pietrzak M,Kuczma M,Simms CP,Kurczewska A,Refugia JM,Lowery DJ,Rempala G,Gutkin D,Ignatowicz L,Muranski P,Kraj P

更新日期：2018-08-28 00:00:00

abstract：:Regulatory T (T(reg)) cells are a unique CD4(+) T cell lineage that plays a crucial role in the maintenance of immunological tolerance. The Forkhead box transcription factor Foxp3 is critically involved in T(reg) cell development and responsible for determining the suppressive function of these cells. The majority of ...

journal_title：Science signaling

authors： Toker A,Huehn J

更新日期：2011-02-01 00:00:00

abstract：:Adenosine 5'-diphosphate (ADP)-ribosylation is a protein posttranslational modification that is catalyzed by ADP-ribosyltransferases (ARTs), using nicotinamide adenine dinucleotide (NAD(+)) as a substrate. Mono-ribosylation can be extended into polymers of ADP-ribose (PAR). Poly(ADP-ribosyl)polymerase (PARP) 1, the be...

journal_title：Science signaling

authors： Hottiger MO,Boothby M,Koch-Nolte F,Lüscher B,Martin NM,Plummer R,Wang ZQ,Ziegler M

更新日期：2011-05-24 00:00:00

abstract：:Inositol pyrophosphates are highly energetic inositol polyphosphate molecules present in organisms from slime molds and yeast to mammals. Distinct classes of enzymes generate different forms of inositol pyrophosphates. The biosynthesis of these substances principally involves phosphorylation of inositol hexakisphospha...

journal_title：Science signaling

authors： Chakraborty A,Kim S,Snyder SH

更新日期：2011-08-23 00:00:00

abstract：:Tools for conducting high-throughput kinome analysis do not exist for many species. For example, two commonly used techniques for monitoring phosphorylation events are phosphorylation-specific antibodies and peptide arrays. The majority of phosphorylation-specific antibodies are for human or mouse targets, and the con...

journal_title：Science signaling

authors： Jalal S,Arsenault R,Potter AA,Babiuk LA,Griebel PJ,Napper S

更新日期：2009-01-20 00:00:00

abstract：:The hypoxia inducible factors (HIFs) and CCAAT/enhancer binding protein alpha (C/EBP alpha) are transcription factors that mediate adaptive responses to hypoxia and control aspects of energy metabolism, respectively. New evidence suggests that when HIF-1 alpha and C/EBP alpha interact, they bring about reciprocal func...

journal_title：Science signaling

authors： Janardhan HP

更新日期：2008-10-28 00:00:00