Abstract:
:The K+/Cl- cotransporter KCC2 is a molecular switch between excitatory and inhibitory effects of GABAergic inputs into neurons. In a pair of exciting studies, Watanabe et al. and Pisella et al. elucidate the role of KCC2 dephosphorylation in this process and reveal its consequences for neurodevelopment and nervous system pathology.
journal_name
Sci Signaljournal_title
Science signalingauthors
Zamponi GWdoi
10.1126/scisignal.aay8960subject
Has Abstractpub_date
2019-10-15 00:00:00issue
603eissn
1945-0877issn
1937-9145pii
12/603/eaay8960journal_volume
12pub_type
评论,杂志文章,评审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
更新日期:2019-11-19 00:00:00
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
更新日期:2016-08-09 00:00:00
abstract::In this issue of Science Signaling, Lu et al reveal a role for Parkin-mediated mitophagy in beige-to-white adipocyte transition. In the absence of Parkin, mitochondria in thermogenic beige adipocytes are preserved even after the elimination of cold mimetic stimuli-in contrast to their typical elimination during the wh...
journal_title:Science signaling
pub_type: 评论,杂志文章,评审
doi:10.1126/scisignal.aat1082
更新日期:2018-04-24 00:00:00
abstract::Ovarian cancer is a complex disease with heterogeneity among the gene expression molecular subtypes (GEMS) between patients. Patients with tumors of a mesenchymal ("Mes") subtype have a poorer prognosis than patients with tumors of an epithelial ("Epi") subtype. We evaluated GEMS of ovarian cancer patients for molecul...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaf8175
更新日期:2016-10-04 00:00:00
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
更新日期:2019-12-17 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
pub_type: 杂志文章
doi:10.1126/scisignal.aar2125
更新日期:2018-08-28 00:00:00
abstract::The prevalence, presentation, and progression of Alzheimer's disease (AD) differ between men and women, although β-amyloid (Aβ) deposition is a pathological hallmark of AD in both sexes. Aβ-induced activation of the neuronal glutamate receptor mGluR5 is linked to AD progression. However, we found that mGluR5 exhibits ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.abd2494
更新日期:2020-12-15 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
pub_type: 杂志文章
doi:10.1126/scisignal.aad9055
更新日期:2016-05-17 00:00:00
abstract::Cyclic-di-GMP (c-di-GMP) is a bacterial second messenger that transduces internal and external signals and regulates bacterial motility and biofilm formation. Some organisms encode more than 100 c-di-GMP-modulating enzymes, but only for a few has a signal been defined that modulates their activity. We developed and ap...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaa1796
更新日期:2015-06-09 00:00:00
abstract::This year's signaling breakthroughs highlight insights into the pathogenesis or treatment of cancer, malaria, and neurodegenerative disorders; reveal molecular insights into cell death; and identify signals that could be leveraged to prevent plant parasitism or engineer bacteria as microbial fuel cells. ...
journal_title:Science signaling
pub_type: 社论
doi:10.1126/scisignal.aad9795
更新日期:2016-01-05 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
pub_type: 杂志文章
doi:10.1126/scisignal.aah3738
更新日期:2018-03-06 00:00:00
abstract::Group 3 innate lymphoid cells (ILC3s) are composed of subsets that are either positive or negative for the natural cytotoxicity receptor (NCR) NKp46 (encoded by Ncr1). ILC3s are located at mucosal sites, such as in the intestine and lung, where they are exposed to billions of commensal microbes and potentially harmful...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaf2176
更新日期:2016-05-03 00:00:00
abstract::Phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins play essential roles in DNA-based and RNA-based processes, such as the response to DNA damage, messenger RNA (mRNA) quality control, transcription, and translation, where they contribute to the maintenance of genome integrity and accurate gene...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000468
更新日期:2010-04-06 00:00:00
abstract::The mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 2 (ERK2) is ubiquitously expressed in mammalian tissues and is involved in a wide range of biological processes. Although MAPKs have been intensely studied, identification of their substrates remains challenging. We have optimized a chem...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002010
更新日期:2011-10-25 00:00:00
abstract::Most metazoans have at least some ability to regenerate damaged cells and tissues, although the regenerative capacity varies depending on the species, organ, or developmental stage. Cell replacement and regeneration occur in two contexts: renewal of spent cells during tissue homeostasis (homeostatic growth), and in re...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.3145re8
更新日期:2010-10-26 00:00:00
abstract::This two-issue series focuses on how understanding how signaling pathways are altered in cancer cells can enable researchers to develop more effective therapies. Cancer is a pleiotropic disease. Tumor cells change over time and, even within a specific tumor, cells may have different mutations and dependencies on diffe...
journal_title:Science signaling
pub_type: 社论
doi:10.1126/scisignal.2004149
更新日期:2013-03-26 00:00:00
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
更新日期:2017-10-24 00:00:00
abstract::Although many anticancer drugs that target receptor tyrosine kinases (RTKs) provide clinical benefit, their long-term use is limited by resistance that is often attributed to increased abundance or activation of another RTK that compensates for the inhibited receptor. To uncover common and unique features in the signa...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2003994
更新日期:2013-07-16 00:00:00
abstract::Cytotoxic lymphocytes share the presence of the activating receptor NK receptor group 2, member D (NKG2D) and the signaling-competent adaptor DNAX-activating protein 10 (DAP10), which together play an important role in antitumor immune surveillance. Ligand stimulation induces the internalization of NKG2D-DAP10 complex...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aab2724
更新日期:2015-10-27 00:00:00
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
更新日期:2009-02-10 00:00:00
abstract::Mutations in ERBB2, the gene encoding epidermal growth factor receptor (EGFR) family member HER2, are common in and drive the growth of "HER2-negative" (not ERBB2 amplified) tumors but are rare in "HER2-positive" (ERBB2 amplified) breast cancer. We analyzed DNA-sequencing data from HER2-positive patients and used cell...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aat9773
更新日期:2018-10-09 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
pub_type: 杂志文章
doi:10.1126/scisignal.aax0715
更新日期:2019-12-03 00:00:00
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
更新日期:2015-04-21 00:00:00
abstract::The deubiquitylating enzyme OTUB1 is present in all tissues and targets many substrates, in both the cytosol and nucleus. We found that casein kinase 2 (CK2) phosphorylated OTUB1 at Ser(16) to promote its nuclear accumulation in cells. Pharmacological inhibition or genetic ablation of CK2 blocked the phosphorylation o...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaa0441
更新日期:2015-04-14 00:00:00
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
更新日期:2015-12-01 00:00:00
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
更新日期:2012-11-27 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
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2002277
更新日期:2011-07-12 00:00:00
abstract::Precise control of the activity and abundance of ubiquitin-conjugating enzymes (E2s) ensures fidelity in ubiquitin chain synthesis. In this issue of Science Signaling, Liess et al. demonstrate that the human anaphase-promoting complex (APC/C)-associated E2 UBE2S adopts an autoinhibited dimeric state that increases the...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.abd9892
更新日期:2020-10-20 00:00:00
abstract::Spontaneous neural differentiation of embryonic stem cells is induced by Noggin-mediated inhibition of bone morphogenetic protein 4 (BMP4) signaling. RhoA is a guanosine triphosphatase (GTPase) that regulates cytoskeletal dynamics and gene expression, both of which control stem cell fate. We found that disruption of S...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaf0791
更新日期:2016-07-26 00:00:00
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
更新日期:2013-07-30 00:00:00