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.
 | Lipid signaling: LPA's ways of actin
Lysophosphatidic acid (LPA) controls actin dynamics indirectly, through cell surface receptor-mediated signaling, and directly, by binding and inhibiting villin.
Original research paper: J. Biol. Chem published online 5 October 2009 (DOI: 10.1074/jbc.M109.012716) |
 | Signaling: A Ras and NF-κB pas de deux
Two studies reveal a crucial role for NF-κB signaling in cancers that possess activating mutations in KRAS.
Original research paper: Nature 462, 104-107 (5 November 2009) |
 | Cancer biology: The benefit of being single
TGFβ signaling drives single cell motility and stimulates hematogenic metastasis in breast cancer cells.
Original research paper: Nature Cell Biology 11, 1287-1296 (2009) |
 | DNA damage: Keeping telomerase at bay
Activation of the DNA-damage response pathway elicits phosphorylation of Pif1, which restrains the activity of telomerase at double-stranded DNA breaks.
Original research paper: Nature Cell Biology 11, 1383-1386 (2009) |
 | Apoptosis: Watching caspase 2 get active
A bimolecular fluorescence (BiFC) approach has revealed that caspase 2 activation in response to heat shock occurs before mitochondrial outer membrane permeabilization.
Original research paper: Mol. Cell 35, 830-840 (2009) |
 | Therapeutic resistance: Smoothing the way
A medulloblastoma tumor that developed resistance to the smoothened (SMO) receptor inhibitor GDC-0449 had acquired a mutation in SMO that blocked GDC-0449 binding without compromising hedgehog pathway activation.
Original research paper: Science 326, 572-574 (2009) |
 | In brief: November 2009
Transcription | 2010 Molecular motors | Innate immunity | Apoptosis | Senescence | Ageing | Neurodegenerative disease | Ion channels | Obesity and diabetes | Memory |
 | Evolution: No turning back
Evolutionary mutations in the glucocorticoid receptor (GR) that imparted selectivity to cortisol cannot be reverted, suggesting that changes in protein function or structure happening over the course of tens of millions of years can prevent molecular turnarounds and render evolution irreversible.
Original research paper: Nature 461, 515-519 (2009) |
 | Metabolic disease: Dual benefit of bile acid receptor agonist
An agonist of G protein-coupled bile acid receptor 1 (GPBAR1; also known as TGR5) is capable of both preventing weight gain and maintaining glucose homeostasis, revealing a possible new treatment for diabetes and obesity.
Original research paper: Cell Metab. 10, 167-177 (2009) |
 | Chromatin: JAK2 goes nuclear
JAK2 phosphorylates the core histone H3, which prevents its interaction with heterochromatin protein 1α (HP1α) and excludes HP1α from chromatin regions near the phosphorylated histone.
Original research paper: Nature 461, 819-822 (2009) |
 | Cancer stem cells: Symmetry is key
The tumor suppressor protein p53 regulates the polarity of mammary stem cell division.
Original research paper: Cell 138, 1083-1095 (2009) |
 | Synaptic plasticity: Astrocytes as regulators
EPHA4–ephrin A3 signaling modulates neuronal plasticity by regulating glutamate transport activity.
Original research paper: Nature Neurosci. 12, 1285-1292 (2009) |
 | Cancer: CpG-siRNA deals double blow to tumours
An oligonucleotide fusion construct consisting of a Toll-like receptor (TLR) agonist joined to small interfering RNA (siRNA) against Stat3 inhibits tumor growth in mouse models.
Original research paper: Nature Biotech. 27, 933-940 (2009) |
 | Bacterial pathogenesis: A 'hijacked' regulatory mechanism
Actin tail formation and consequent cell-to-cell spread of the pathogen L. monocytogenes is regulated by casein kinase 2 (CK2)-mediated phosphorylation of a bacterial protein that mimics the action of Wiscott-Aldrich syndrome protein (WASP).
Original research paper: Cell Host Microbe 6, 268-278 (2009) |
 | Autophagy: Autophagy takes an alternative route
Mammalian autophagy can occur through a canonical ATG5- and ATG7-dependent pathway, as well as through an alternative ATG5- and ATG7-independent pathway.
Original research paper: Nature 461, 654-658 (2009) |
 | Immune regulation: TReg cells offer a bespoke service
STAT3 expression by TReg cells is required for the control of TH17 cell responses.
Original research paper: Science 1 October 2009 (doi: 10.1126/science.1172702) |
 | Genetics: An unanticipated role
Polycomb group (PcG) proteins are thought to have an oncogenic role in human cancer, but two studies in Drosophila melanogaster have shown that PcG proteins can also function as tumor suppressors by repressing key oncogenic signaling pathways.
Original research paper: Nature Genet. 41, 1076-1082 (2009) |
 | Psychiatric disorders: DISC1 drives development through girdin
An interaction between disrupted in schizophrenia 1 (DISC1) and the actin-binding protein girdin is important for DISC1-mediated regulation of neuronal growth and migration in the postnatal and adult hippocampus.
Original research paper: Neuron 63, 761-773 (2009) |
 | Cell biology: A fluid situation
Fluid flow in moving cells can be measured by monitoring the size-dependence of particle distribution in the lamellipodium.
Original research paper: Nat. Cell Biol. 11, 1219-1224 (2009) |
 | Cell signalling: A new MAP for miRNAs
Activation of the MAPK–ERK pathway stabilizes the microRNA-generating complex, which enhances the capacity for microRNA biogenesis.
Original research paper: Cell 139, 112-122 (2009) |
 | Hypoxia: HIF1 in opposition
HIF1α induces the expression of the microRNA mir-210, which in turn regulates the levels of several genes that seem to be required for the initial growth phase of xenografted cancer cell lines.
Original research paper: Mol. Cell 35, 856-867 (2009) |
 | Therapy: Swings and roundabouts
A mouse model of juvenile myelomonocytic leukemia (JMML), in which the tumor suppressor Nf1 is deleted in bone marrow cells, has revealed a potential mechanism by which this cancer develops resistance to MEK inhibitors.
Original research paper: Nature 461, 411-414 (2009) |
 | Development: Remembering Hedgehog
The response of the Drosophila wing imaginal disc to Hedgehog (HH) depends not so much on the local concentration of HH, but rather on their past history of exposure to this morphogen.
Original research paper: PLoS Biol. 7, e1000202 (2009) |
 | Mood disorders: Antidepressant action through gene regulation
Inhibitors of histone deacetylases (HDACs) — enzymes that affect the acetylation status of histones and regulate the remodeling of chromatin — have antidepressant actions.
Original research paper: J. Neurosci. 29, 11451-11460 (2009) |
