These short, accessible highlights summarize and contextualize must-read papers related to cell signaling. These articles add background and context to summaries of primary research. 'In brief' articles emphasize key aspects of selected articles.
 | GPCRs: Adrenergic receptor gets bent out of shape by morphine
Morphine inhibits adrenergic receptor signaling by inducing a trans-conformational switch in the α2A-adrenergic receptor (α2A-AR) when in a complex with the morphine receptor, MOR.
Original research paper: Nature Chemical Biology 4, 126-131 (2008) |
 | Angiogenesis: PGC-1α provides a breath of fresh air
The transcriptional coactivator PGC-1α and transcription factor ERR-α stimulate angiogenesis in hypoxic conditions by directly upregulating VEGF expression.
Original research paper: Nature 451, 1008-1012 (2008) |
 | Ethylene signaling: MAPKing new pathways
Two antagonistic MAPK pathways regulate ethylene signaling in plants through differential phosphorylation of the transcription factor EIN3.
Original research paper: Nature 451, 789-795 (2008) |
 | Tumor cell invasion: It's not just ROCK 'n' Rho
The kinase PDK1 promotes cancer cell migration and invasion by blocking the interaction between RhoE and ROCK1.
Original research paper: Nature Cell Biology 10, 127-137 (2008) |
 | Signaling cross-talk: Pyk-ing the pathway for STAT activation
The calcium-dependent kinase Pyk2 coordinates both interferon-α signaling and calcium signaling in the regulation of Jak1 and STAT1 activation.
Original research paper: Nature Immunology 9, 186-193 (2008) |
 | Chromosome segregation: Tension rules
Shugoshin proteins regulate centromeric cohesion during mitosis and meiosis to protect sister chromatids from being prematurely segregated.
Original research paper: Nature Cell Biol. 10, 42-52 (2008) |
 | Tumour immunotherapy: Little pig, little pig, let me come in
When the endothelin B receptor (ETBR) is highly expressed in the tumor endothelium it blocks T-cell homing, suggesting that pharmacologic inhibition of ETBR might cause immunotherapy-induced T cells to gain access to the tumor.
Original research paper: Nature Med. 14, 28-36 (2008) |
 | In brief: February 2008
Lipids | Cell proliferation | Inflammation | T-cell activation | Mouse models | Tumour suppressors | Repair | Local protein synthesis | Kinase inhibitors | Cell biology | Biophysics | Structural biology |
 | Stem cells: Safeguarding pluripotency
The transcription factor Nanog safeguards pluripotent cells against premature differentiation and plays a central role in the production of germ cells.
Original research paper: Nature 450, 1230-1234 (2007) |
 | Neurological disorders: A fragile balance
Excessive activation of group-1 metabotropic glutamate receptors (mGluRs) reproduces many neurological features of Fragile X syndrome, and compounds that block mGluR signaling may be useful for treating the disease.
Original research paper: Neuron 56, 955-962 (2007) |
 | Gene regulation: Gathering a bouquet of miRNA targets
An efficient and robust biochemical screen for microRNAs and their targeted mRNAs allows unprecedented in vivo characterization of microRNA-regulated genes.
Original research paper: Mol. Cell 28, 598-613 (2007) |
 | Lipids: Cofilin set free
EGF signaling reduces PtdIns(4,5)P2 levels, which relieves cofilin from PtdIns(4,5)P2-mediated sequestration at the plasma membrane and permits its relocalization to the leading edge of newly formed lamellipodia.
Original research paper: J. Cell Biol. 179, 1247-1259 (2007) |
 | Tumour immunology: TGFβ betrays immunity for tumorigenesis
Mammary tumors deficient in the type II TGF-β receptor recruit myeloid cells that produce TGF-β1 and matrix metalloproteinases, which facilitate tumor invasion and metastasis.
Original research paper: Cancer Cell 13, 23-35 (2008) |
 | Signalling: Structural survey
The crystal structure of the p110α catalytic subunit of PI3K in complex with the p85α regulatory subunit illuminates the mechanisms by which p110α oncogenic mutations activate the protein.
Original research paper: Science 318, 1744-1748 (2007) |
 | Chromatin: CENP-B-mediated genome-wide surveillance
CENP-B homologs protect somatic cell genomes from RNA-based transposable elements by recruiting chromatin modifiers that repress existing transposable elements, and by blocking homologous recombination to prevent new mobile-element integration into the host genome.
Original research paper: Nature 451, 431-436 (2008) |
 | Anticancer drugs: Reversing resistance
The small molecule obatoclax inhibits pro-survival BCL2 family members, thus restoring the sensitivity of drug-resistant tumors to several new anticancer drugs.
Original research paper: Proc. Natl Acad. Sci. USA 104, 19512-19517 (2007) |
 | Lipids: Orientating with PtdIns(3,4,5)P3
PtdIns(3,4,5)P3 orients the spindle during mitosis by aligning the direction of the dynein–dynactin motor complexes.
Original research paper: Dev. Cell 13, 796-811 (2007) |
 | Innate immunity: NF-κB is not alone
Akirin is a novel nuclear factor that functions in parallel with NF-κB to regulate innate immune responses in mice and flies.
Original research paper: Nature Immunol. 9, 97-104 (2008) |
 | Tumorigenesis: First or last?
In mouse models, the loss of the TRAIL receptor differentially promotes tumorigenesis depending on tissue type, suggesting that TRAIL mimetics could be therapeutically relevant at specific stages of several different cancers.
Original research paper: J. Clin. Invest. 118, 100-110 (2007) |
 | Behaviour: Mating games
Two studies in Drosophila explore the effect of sex peptide receptor and genderblind — a glial protein that is involved in glutamate secretion — in regulating mating behavior.
Original research paper: Nature 451, 33-37 (2008) |
 | Chemogenomics: A change of tactic
A small-molecule antagonist of the somatostatin receptor 5 (sst5) was uncovered by a focused screen of drugs with known affinity for receptors with a similar ligand-binding site, validating this approach for the discovery of new pharmacologic modulators of receptor function.
Original research paper: J. Med. Chem. 50, 6291-6294 (2007) |
 | Membrane trafficking: Efficient recycling
Five studies now show that retromer-dependent recycling of the transmembrane protein Wntless regulates Wnt secretion by maintaining a steady supply of Wntless in the Golgi.
Original research paper: Dev. Cell 14, 132-139 (2008) |
 | Cell signalling: Balancing act
The transcription factor E2F1 transactivates different subsets of target genes to orchestrate either proliferation or apoptosis through differential activation of the PI3K–Akt pathway.
Original research paper: Cancer Cell 13, 11-22 (2008) |
 | Cell death: ...and a nice Chianti
Entosis, a form of non-apoptotic cell death in which one cell is completely internalized within another cell, requires activation of the Rho–ROCK pathway and upregulation of myosin II activity in the internalizing cell.
Original research paper: Cell 131, 966-979 (2007) |
 | Protein homeostasis: External influence
A mutation in a neuron-specific regulator of GABA synthesis causes defective GABAergic signaling and impairs muscular coordination by fostering the premature conversion of soluble polyglutamine-containing proteins to an aggregated form in muscle cells.
Original research paper: Genes Dev. 21, 3006-3016 (2007) |
 | Anticancer drugs: Redesigning kinase inhibitors
A re-engineered version of the kinase inhibitor imatinib retains its potent activity against gastrointestinal stromal tumors but exhibits reduced cardiac toxicity, suggesting that modifying other kinase inhibitors could increase their safety and efficacy.
Original research paper: J. Clin. Invest. 117, 4044-4054 (2007) |
 | Cell polarity: Heads or tails?
The Wnt/β-catenin signaling pathway maintains the anterioposterior identity of flatworms during regeneration and homeostasis; inhibiting this pathway following tail amputation results in the regeneration of a head in the tail position.
Original research paper: Science 319, 323-327 (2008) |
 | Innate immunity: TAMing inflammation
TLR signaling is regulated by a negative-feedback circuit whereby activation of TLR upregulates expression of the Tyro3, Axl and Mer (TAM) receptor tyrosine kinases, which block further TLR-mediated signaling.
Original research paper: Cell 131, 1124-1136 (2007) |
 | Drug resistance: Destabilizing influence
Low expression of TGFBI corresponds to resistance to the drug paclitaxel in an ovarian cancer cell line, suggesting that TGFBI could be used as a biomarker for predicting chemotherapy response.
Original research paper: Cancer Cell 12, 514-527 (2007) |
 | Sensory perception: One TRPM8 fits all
Neuronal expression studies on the TRPM8 ion channel reveal that the ability of TRPM8 to convey different sensations of cold depends on its expression in several discrete types of sensory neurons.
Original research paper: J. Neurosci. 27, 14147-14157 (2007) |
 | Malaria: Malaria eats out
The malarial parasite Plasmodium falciparum escapes from host red blood cells by activating a cascade of proteases; inhibiting the parasitic PfSUB1 serine protease blocks Plasmodium egress, opening a new avenue for the development of anti-malarial therapies.
Original research paper: Cell 131, 1072-1083 (2007) |
