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.
 | Ion transporters: A new Cu-lprit for tyrosinase activation in melanosomes
The copper transporter ATP7A is required for tyrosinase activity and melanin production in melanosomes.
Original research paper: Nature 454, 1142-1146 (2008) |
 | Cell cycle: Coming together to tear cells apart
The sequential phosphorylation of PKCε is necessary for its association with 14-3-3 proteins and its localization to the mitotic cleavage furrow, as well as the subsequent dissolution of the mitotic ring and the separation of daughter cells during mitosis.
Original research paper: Nature Cell Biology 10, 891-901 (2008) |
 | Polycystic kidney disease: The TNF-α connection
TNF-α-mediated induction of FIP2 causes mislocalization of polycystin-2 and potentiates the development of autosomal dominant polycystic kidney disease.
Original research paper: Nature Medicine 14, 863-868 (2008) |
 | PI(3)K signaling: Separate but not equal
The kinase activity of the PI(3)K subunit p110β is linked to the oncogenic transformation of mouse prostate epithelium, whereas a second, kinase-independent activity regulates cellular proliferation and signaling downstream of tyrosine-kinase receptors.
Original research paper: Nature 454, 776-779 (2008) |
 | Immunology: Arrestin cytotoxic pathway activation
β-arrestin 2 negatively regulates natural killer (NK) cell cytotoxicity by facilitating recruitment of Src homology-containing tyrosine phosphatases (SHPs) to inhibitory NK cell receptors.
Original research paper: Nature Immunology 9, 898-907 (2008) |
 | Inflammation: Lysosomes spill the signal
Phagocytosis of peptide amyloid-β aggregates causes lysosomal rupture and the release of proteases into the cytoplasm, which induces activation of the NALP3 inflammasome and the maturation of interleukin-1β.
Original research paper: Nature Immunol. 9, 847-856 (2008) |
 | Tumorigenesis: PUMA strikes again
Loss of Puma (p53-upregulated mediator of apoptosis) in conjunction with overexpression of the Myc oncogene accelerates tumor development in a murine model of Burkitt lymphoma.
Original research paper: Mol. Cell. Biol. 28, 5391-5402 (2008) |
 | In brief: August 2008
Cell polarity | Membrane trafficking | Neuroimmunology | Tumour biology | B-cell responses | Angiogenesis | Biomarkers | Gene regulation | Development | Addiction | Stress response | Sensory systems | Sensory systems | Axon guidance | G-protein-coupled receptors |
 | Stroke: Widening the therapeutic window?
Inhibition of the platelet-derived growth factor receptor-α (PDGFR-α) helps maintain the integrity of the blood–brain barrier and reduces hemorrhagic complications in a mouse model of ischemic stroke.
Original research paper: Nature Med. 14, 731-737 (2008) |
 | Chemical biology: Talk among histones
The use of chemically synthesized and ubiquitinated histone subunits has revealed that the ubiquitinated histone H2B directly stimulates Dot1-mediated methylation of histone H3 at Lys 79.
Original research paper: Angew. Chem. Int. Ed. Engl. 46, 2814-2818 (2007) |
 | Bacterial physiology: From start to finish for Streptomyces
A complete signaling cascade — from nutrient sensing to antibiotic biosynthesis — has been described for Streptomyces coelicolor.
Original research paper: EMBO Rep. 9, 670-675 (2008) |
 | Cell cycle: Achieving entry
Bora, a protein that participates in asymmetric cell division, works with the kinase Aurora A to synergistically activate Polo-like kinase-1 (PLK1) and induce mitotic entry in somatic cells.
Original research paper: Science 320, 1655-1658 (2008) |
 | Angiogenesis: Turning it down a Notch
Inhibition of Notch1 signaling in vascular endothelial growth factor (VEGF)-producing tumor cells reduces tumor volume and decreases angiogenesis.
Original research paper: Cancer Res. 68, 4727-4735 (2008) |
 | Therapeutics: Unravelling lethality
Two studies provide insight into how drugs that target topoisomerases are able to induce apoptosis in cancer cells.
Original research paper: Mol. Cell 30, 790-802 (2008) |
 | Neurological disorders: Magic with rapamycin
Mutations in tuberous sclerosis complex 2 (TSC2) causes mental retardation, seizures and behavioral problems, but treating Tsc2+/- mice with the mTOR inhibitor rapamycin improves learning and memory.
Original research paper: Nature Med. 14, 843-848 (2008) |
 | Biofilms: Clutch control
The motility of B. subtilis cells within biofilms is shut down through the use of a molecular 'clutch' protein, EpsE, which disables the flagellar motor.
Original research paper: Science 320, 1636-1638 (2008) |
 | Cell signalling: Sensing nutrient availability
Rag GTPases functionally interact with mTOR complex-1 (mTORC1) and are necessary for the activation of the mTORC1 pathway by amino acids.
Original research paper: Science 320, 1496-1501 (2008) |
 | T-cell activation: Adaptive cholesterol
Liver X receptor (LXR), a nuclear receptor that has a key role in lipid metabolism, represses T-cell activation, thus linking cholesterol biosynthesis with the aquired immune response.
Original research paper: Cell 134, 97-111 (2008) |
 | Angiogenesis: TGFβ makes a new friend
Prostaglandin E2 (PGE2) signals through metalloproteinases and SMAD3 to enhance transforming growth factor β (TGFβ) activation.
Original research paper: Blood 112, 1120-1128 (2008) |
 | Neurodegenerative diseases: Clearing up Aβ
Amyloid-β degradation can be enhanced by activation of the plasmin protease cascade or increased lipidation of apolipoprotein E (ApoE).
Original research paper: Proc. Natl Acad. Sci. USA 105, 8754-8759 (2008) |
 | Stem cells: Induced pluripotency: is there a silver bullet?
Small molecules can replace some of the genetic factors required for the generation of induced pluripotent stem (iPS) cells.
Original research paper: Nat. Biotechnol. 26, 795-797 (2008) |
 | Membrane trafficking: All cisternae are not created equal
A novel 'membrane partitioning' model of membrane trafficking posits that Golgi enzymes and transmembrane cargo are rapidly partitioned between two distinct lipid phases of a continuous Golgi stack, with a high rate of exchange among the cisternae.
Original research paper: Cell 133, 1055-1067 (2008) |
 | Leukaemia: Mixed up
A mouse model of mixed-lineage leukemia has revealed that inhibition of the GTPase Rac results in cell cycle arrest and apoptosis, with a concomitant increase in BCL-XL degradation.
Original research paper: Cancer Cell 13, 483-495 (2008) |
 | Synaptic plasticity: Retrograde signal is the way forward
Serotonin activates G-protein-coupled receptors to trigger an increase in Ca2+ and the release of one or more retrograde signals that mediate presynaptic expression of the sensorin neuropeptide, leading to long-term changes in synaptic strength.
Original research paper: Curr. Biol. 18, 920-925 (2008) |
 | Proteases: Novel route to protease targeting
A subset of non-steroidal anti-inflammatory drugs (NSAIDs) selectively binds to the amyloid precursor protein (APP) and reduce levels of the 42-residue isoform of the amyloid-β peptide that has been implicated in Alzheimer's disease pathogenesis.
Original research paper: Nature 453, 925-929 (2008) |
 | Imaging and visualization: A time stamp for proteins
A self-cleaving protein tag simplifies the labeling and visualization of newly synthesized target proteins in tissue and whole animals.
Original research paper: Proc. Natl. Acad. Sci. USA 105, 7744-7749 (2008) |
 | Cell signalling: AKTing in Wnt pathway
Nucleo-cytoplasmic trafficking of β-catenin is regulated by the formation of a trimolecular complex between itself and the proteins 14-3-3 and Chibby.
Original research paper: J. Cell Biol. 181, 1141-1154 (2008) |
 | Inflammation: A crucial cut
The neutrophil-derived serine proteases proteinase-3 and elastase cooperate to cleave the anti-inflammatory factor progranulin, thereby inactivating it and promoting neutrophil activation and inflammation.
Original research paper: J. Clin. Invest. 118, 2438-2447 (2008) |
 | Angiogenesis: Survival of the infected
Kaposi sarcoma-associated herpes virus (KSHV) infection confers a survival and angiogenic advantage to endothelial cells by activating the PI3K–Akt–mTOR pathway.
Original research paper: Cancer Res. 68, 4640-4648 (2008) |
 | Dendrites: Ras puts on a spread
Ras can be activated by synaptic activity in a single dendritic spine, which causes it to diffuse out of that spine and alter synaptic function in neighboring spines.
Original research paper: Science 321, 136-140 (2008) |
 | Spectroscopy: Surviving the gas phase
Researchers have identified experimental conditions that permit membrane-bound protein complexes to survive the gas phase of mass spectrometry, thus enabling studies into protein topology, subunit stoichiometry and ligand binding.
Original research paper: Science 321, 243-246 (2008) |
