The basis for the distinct biological activities of vascular endothelial growth factor receptor-1 ligands.

Abstract:

:Vascular endothelial growth factors (VEGFs) regulate blood and lymphatic vessel development through VEGF receptors (VEGFRs). The VEGFR immunoglobulin homology domain 2 (D2) is critical for ligand binding, and D3 provides additional interaction sites. VEGF-B and placenta growth factor (PlGF) bind to VEGFR-1 with high affinity, but only PlGF is angiogenic in most tissues. We show that VEGF-B, unlike other VEGFs, did not require D3 interactions for high-affinity binding. VEGF-B with a PlGF-derived L1 loop (B-L1P) stimulated VEGFR-1 activity, whereas PlGF with a VEGF-B-derived L1 loop (P-L1B) did not. Unlike P-L1B and VEGF-B, B-L1P and PlGF were also angiogenic in mouse skeletal muscle. Furthermore, B-L1P also bound to VEGFR-2 and activated downstream signaling. These results establish a role for L1-mediated D3 interactions in VEGFR activation in endothelial cells and indicate that VEGF-B is a high-affinity VEGFR-1 ligand that, unlike PlGF, cannot efficiently induce signaling downstream of VEGFR-1.

journal_name

Sci Signal

journal_title

Science signaling

authors

Anisimov A,Leppänen VM,Tvorogov D,Zarkada G,Jeltsch M,Holopainen T,Kaijalainen S,Alitalo K

doi

10.1126/scisignal.2003905

subject

Has Abstract

pub_date

2013-07-02 00:00:00

pages

ra52

issue

282

eissn

1945-0877

issn

1937-9145

pii

6/282/ra52

journal_volume

6

pub_type

杂志文章
  • Loss of MCU prevents mitochondrial fusion in G1-S phase and blocks cell cycle progression and proliferation.

    abstract::The role of the mitochondrial Ca2+ uniporter (MCU) in physiologic cell proliferation remains to be defined. Here, we demonstrated that the MCU was required to match mitochondrial function to metabolic demands during the cell cycle. During the G1-S transition (the cycle phase with the highest mitochondrial ATP output),...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aav1439

    authors: Koval OM,Nguyen EK,Santhana V,Fidler TP,Sebag SC,Rasmussen TP,Mittauer DJ,Strack S,Goswami PC,Abel ED,Grumbach IM

    更新日期:2019-04-30 00:00:00

  • Differential regulation of Ca2+ influx by ORAI channels mediates enamel mineralization.

    abstract::Store-operated Ca2+ entry (SOCE) channels are highly selective Ca2+ channels activated by the endoplasmic reticulum (ER) sensors STIM1 and STIM2. Their direct interaction with the pore-forming plasma membrane ORAI proteins (ORAI1, ORAI2, and ORAI3) leads to sustained Ca2+ fluxes that are critical for many cellular fun...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aav4663

    authors: Eckstein M,Vaeth M,Aulestia FJ,Costiniti V,Kassam SN,Bromage TG,Pedersen P,Issekutz T,Idaghdour Y,Moursi AM,Feske S,Lacruz RS

    更新日期:2019-04-23 00:00:00

  • The HIF-1 alpha-C/EBP alpha axis.

    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

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.143jc2

    authors: Janardhan HP

    更新日期:2008-10-28 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

  • Brx mediates the response of lymphocytes to osmotic stress through the activation of NFAT5.

    abstract::Extracellular hyperosmolarity, or osmotic stress, generally caused by differences in salt and macromolecule concentrations across the plasma membrane, occurs in lymphoid organs and at inflammatory sites. The response of immune cells to osmotic stress is regulated by nuclear factor of activated T cells 5 (NFAT5), a tra...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2000081

    authors: Kino T,Takatori H,Manoli I,Wang Y,Tiulpakov A,Blackman MR,Su YA,Chrousos GP,DeCherney AH,Segars JH

    更新日期:2009-02-10 00:00:00

  • Corticosteroid receptor balance regulates life and death in cardiomyocytes.

    abstract::Mineralocorticoid receptor (MR) antagonists are effective at treating heart failure. In this issue of Science Signaling, Oakley et al. provide new insight into their cardioprotective actions and highlight the importance of the opposing relationship between the MR and the related glucocorticoid receptor (GR) in the res...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.aaw8715

    authors: Chapman KE

    更新日期:2019-04-16 00:00:00

  • MicroRNAs add an additional layer to the complexity of cell signaling.

    abstract::MicroRNAs (miRNAs), key posttranscriptional regulators of many biological processes, have been implicated in many diseases, including cancer. In a recent paper, Avraham and colleagues take a systems biology approach to determine whether and how miRNAs are involved in the regulation of oncogenic signaling networks down...

    journal_title:Science signaling

    pub_type: 评论,杂志文章,评审

    doi:10.1126/scisignal.2002182

    authors: Herschkowitz JI,Fu X

    更新日期:2011-07-26 00:00:00

  • Redundant and specialized roles for diacylglycerol kinases α and ζ in the control of T cell functions.

    abstract::The diacylglycerol kinases (DGKs) attenuate diacylglycerol (DAG)-mediated signals by catalyzing the conversion of DAG to phosphatidic acid. In T lymphocytes, the antigen-stimulated generation of DAG links signal strength to the intensity and duration of signaling by the Ras-extracellular signal-regulated kinase (ERK) ...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.aaa0974

    authors: Mérida I,Andrada E,Gharbi SI,Ávila-Flores A

    更新日期:2015-04-28 00:00:00

  • Chemoattractant receptors and leukocyte recruitment: more than cell migration.

    abstract::Chemoattractants induce cell migration through the activation of a distinct family of structurally related heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors. Over the past few years, several receptors in this family have been identified that recognize different classes of chemoattractants...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.259pe10

    authors: Borroni EM,Bonecchi R,Mantovani A,Locati M

    更新日期:2009-02-24 00:00:00

  • mGluR5 antagonism increases autophagy and prevents disease progression in the zQ175 mouse model of Huntington's disease.

    abstract::Huntington's disease (HD) is a neurodegenerative disease caused by an expansion in the huntingtin protein (also called Htt) that induces neuronal cell death with age. We found that the treatment of 12-month-old symptomatic heterozygous and homozygous zQ175 huntingtin knockin mice for 12 weeks with CTEP, a negative all...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aan6387

    authors: Abd-Elrahman KS,Hamilton A,Hutchinson SR,Liu F,Russell RC,Ferguson SSG

    更新日期:2017-12-19 00:00:00

  • How Ca2+-permeable AMPA receptors, the kinase PKA, and the phosphatase PP2B are intertwined in synaptic LTP and LTD.

    abstract::Both synaptic long-term potentiation (LTP) and long-term depression (LTD) are thought to be critical for memory formation. Dell'Acqua and co-workers now demonstrate that transient postsynaptic incorporation of Ca(2+)-permeable (CP) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is required for...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.aaf7067

    authors: Hell JW

    更新日期:2016-04-26 00:00:00

  • Genome to kinome: species-specific peptide arrays for kinome analysis.

    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

    pub_type: 杂志文章

    doi:10.1126/scisignal.254pl1

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

    更新日期:2009-01-20 00:00:00

  • G protein-coupled receptors, cholinergic dysfunction, and Abeta toxicity in Alzheimer's disease.

    abstract::The beta-amyloid (Abeta) peptide is associated with the pathogenesis of Alzheimer's disease (AD). Evidence gathered over the last two decades suggests that the gradual accumulation of soluble and insoluble Abeta peptide species triggers a cascade of events that leads to the clinical manifestation of AD. Abeta accumula...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.293re8

    authors: Thathiah A,De Strooper B

    更新日期:2009-10-20 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

  • The second messenger c-di-AMP inhibits the osmolyte uptake system OpuC in Staphylococcus aureus.

    abstract::Staphylococcus aureus is an important opportunistic human pathogen that is highly resistant to osmotic stresses. To survive an increase in osmolarity, bacteria immediately take up potassium ions and small organic compounds known as compatible solutes. The second messenger cyclic diadenosine monophosphate (c-di-AMP) re...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf7279

    authors: Schuster CF,Bellows LE,Tosi T,Campeotto I,Corrigan RM,Freemont P,Gründling A

    更新日期:2016-08-16 00:00:00

  • Metabotropic glutamate receptors and fragile x mental retardation protein: partners in translational regulation at the synapse.

    abstract::Fragile X syndrome (FXS) mental retardation is caused by loss-of-function mutations in an RNA-binding protein, fragile X mental retardation protein (FMRP). Previous studies in patients or animal models of FXS have identified alterations in dendritic spine structure, as well as synaptic plasticity induced by metabotrop...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/stke.15pe6

    authors: Ronesi JA,Huber KM

    更新日期:2008-02-05 00:00:00

  • Regulation of the 26S proteasome complex during oxidative stress.

    abstract::The proteasome plays a pivotal role in the cellular response to oxidative stress. Here, we used biochemical and mass spectrometric methods to investigate structural changes in the 26S proteasomes from yeast and mammalian cells exposed to hydrogen peroxide (H₂O₂). Oxidative stress induced the dissociation of the 20S co...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2001232

    authors: Wang X,Yen J,Kaiser P,Huang L

    更新日期:2010-12-07 00:00:00

  • Dynamic palmitoylation controls the microdomain localization of the DKK1 receptors CKAP4 and LRP6.

    abstract::Dickkopf1 (DKK1) was originally identified as an antagonist of Wnt signaling that binds to and induces the clathrin-mediated endocytosis of the Wnt coreceptors low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6). DKK1 also binds to cytoskeleton-associated protein 4 (CKAP4), which was originally identifi...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aat9519

    authors: Sada R,Kimura H,Fukata Y,Fukata M,Yamamoto H,Kikuchi A

    更新日期:2019-11-19 00:00:00

  • Long-term potentiation modulates synaptic phosphorylation networks and reshapes the structure of the postsynaptic interactome.

    abstract::The postsynaptic site of neurons is composed of more than 1500 proteins arranged in protein-protein interaction complexes, the composition of which is modulated by protein phosphorylation through the actions of complex signaling networks. Components of these networks function as key regulators of synaptic plasticity, ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf6716

    authors: Li J,Wilkinson B,Clementel VA,Hou J,O'Dell TJ,Coba MP

    更新日期:2016-08-09 00:00:00

  • The Src family kinase Fgr is a transforming oncoprotein that functions independently of SH3-SH2 domain regulation.

    abstract::Fgr is a member of the Src family of nonreceptor tyrosine kinases, which are overexpressed and constitutively active in many human cancers. Fgr expression is restricted to myeloid hematopoietic cells and is markedly increased in a subset of bone marrow samples from patients with acute myeloid leukemia (AML). Here, we ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aat5916

    authors: Shen K,Moroco JA,Patel RK,Shi H,Engen JR,Dorman HR,Smithgall TE

    更新日期:2018-10-23 00:00:00

  • Airway relaxation mechanisms and structural basis of osthole for improving lung function in asthma.

    abstract::Overuse of β2-adrenoceptor agonist bronchodilators evokes receptor desensitization, decreased efficacy, and an increased risk of death in asthma patients. Bronchodilators that do not target β2-adrenoceptors represent a critical unmet need for asthma management. Here, we characterize the utility of osthole, a coumarin ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aax0273

    authors: Wang S,Xie Y,Huo YW,Li Y,Abel PW,Jiang H,Zou X,Jiao HZ,Kuang X,Wolff DW,Huang YG,Casale TB,Panettieri RA Jr,Wei T,Cao Z,Tu Y

    更新日期:2020-11-24 00:00:00

  • Measurement of phosphorylated extracellular signal-regulated kinase 1 and 2 in an undergraduate teaching laboratory with ALPHAscreen technology.

    abstract::Teaching the practical aspects of signal transduction to large undergraduate classes can be challenging when there is only a finite time frame in which to engage in laboratory activities. This teaching resource describes the use of bead-based ALPHAscreen technology for a class of 300 second-year biochemistry students,...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.262tr1

    authors: Hay DL

    更新日期:2009-03-17 00:00:00

  • Convergence of Wnt, growth factor, and heterotrimeric G protein signals on the guanine nucleotide exchange factor Daple.

    abstract::Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades, and their dysregulation plays an integral role in cancer progression. Three cascades that contribute to oncogenic potential are those mediated by Wnt proteins and the receptor Frizzled (FZD), growth factor receptor ty...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aao4220

    authors: Aznar N,Ear J,Dunkel Y,Sun N,Satterfield K,He F,Kalogriopoulos NA,Lopez-Sanchez I,Ghassemian M,Sahoo D,Kufareva I,Ghosh P

    更新日期:2018-02-27 00:00:00

  • Full focus on calcium.

    abstract::Intracellular calcium (Ca2+) signals are of prime importance for cellular function and behavior and are underpinned by a plethora of Ca2+ channels, pumps, transporters, and binding proteins that are regulated in complex ways. A series of biennial meetings, the International Meetings of the European Calcium Society (EC...

    journal_title:Science signaling

    pub_type:

    doi:10.1126/scisignal.aaz0961

    authors: Parys JB,Guse AH

    更新日期:2019-09-17 00:00:00

  • cAMPr: A single-wavelength fluorescent sensor for cyclic AMP.

    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

    pub_type: 杂志文章

    doi:10.1126/scisignal.aah3738

    authors: Hackley CR,Mazzoni EO,Blau J

    更新日期:2018-03-06 00:00:00

  • Inhibition of the kinase ITK in a mouse model of asthma reduces cell death and fails to inhibit the inflammatory response.

    abstract::Interleukin-2 (IL-2)-inducible T cell kinase (ITK) mediates T cell receptor (TCR) signaling primarily to stimulate the production of cytokines, such as IL-4, IL-5, and IL-13, from T helper 2 (TH2) cells. Compared to wild-type mice, ITK knockout mice are resistant to asthma and exhibit reduced lung inflammation and dec...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aab0949

    authors: Sun Y,Peng I,Webster JD,Suto E,Lesch J,Wu X,Senger K,Francis G,Barrett K,Collier JL,Burch JD,Zhou M,Chen Y,Chan C,Eastham-Anderson J,Ngu H,Li O,Staton T,Havnar C,Jaochico A,Jackman J,Jeet S,Riol-Blanco L,Wu

    更新日期:2015-12-01 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

  • Subtle modifications to oxytocin produce ligands that retain potency and improved selectivity across species.

    abstract::Oxytocin and vasopressin mediate various physiological functions that are important for osmoregulation, reproduction, cardiovascular function, social behavior, memory, and learning through four G protein-coupled receptors that are also implicated in high-profile disorders. Targeting these receptors is challenging beca...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aan3398

    authors: Muttenthaler M,Andersson Å,Vetter I,Menon R,Busnelli M,Ragnarsson L,Bergmayr C,Arrowsmith S,Deuis JR,Chiu HS,Palpant NJ,O'Brien M,Smith TJ,Wray S,Neumann ID,Gruber CW,Lewis RJ,Alewood PF

    更新日期:2017-12-05 00:00:00

  • Manganese promotes the aggregation and prion-like cell-to-cell exosomal transmission of α-synuclein.

    abstract::The aggregation of α-synuclein (αSyn) is considered a key pathophysiological feature of certain neurodegenerative disorders, collectively termed synucleinopathies. Given that a prion-like, cell-to-cell transfer of misfolded αSyn has been recognized in the spreading of αSyn pathology in synucleinopathies, we investigat...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aau4543

    authors: Harischandra DS,Rokad D,Neal ML,Ghaisas S,Manne S,Sarkar S,Panicker N,Zenitsky G,Jin H,Lewis M,Huang X,Anantharam V,Kanthasamy A,Kanthasamy AG

    更新日期:2019-03-12 00:00:00

  • Visualizing immune system complexity.

    abstract::The European Molecular Biology Organization (EMBO) meeting Visualizing Immune System Complexity, held in January 2009, covered multiple scales, from imaging single molecules to imaging whole animals. In addition to experimental details, there was an emphasis on modeling both for data analysis and as a predictive tool ...

    journal_title:Science signaling

    pub_type:

    doi:10.1126/scisignal.266mr4

    authors: Dustin ML

    更新日期:2009-04-14 00:00:00