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.
 | IGF binding proteins: Make another little piece of my heart now, baby
Insulin-like growth-factor-binding protein 4 (IGFBP-4) promotes cardiac development by binding to Wnt co-receptors and inhibiting canonical Wnt signaling.
Original research paper: Nature 454, 345-349 (2008) |
 | Post-translational modifications: The active TGF-β receptor is sumoylated
Transforming growth factor-β receptor type I is sumoylated, which regulates Smad3 activation and affects invasion and metastasis.
Original research paper: Nature Cell Biology 10, 654-664 (2008) |
 | Cell cycle: Spinning a transcription factor web
A cyclin-CDK-independent network involving successive waves of transcription factor activity regulates the periodic expression of a significant proportion of cell cycle genes.
Original research paper: Nature 453, 944-947 (2008) |
 | Toll-like receptor signaling: IRAK2 stays the course
The interleukin-1 receptor-associated kinase 2 (IRAK2) is dispensable in the early phase of Toll-like receptor signaling but is required for sustained NF-κB activity.
Original research paper: Nature Immunology 9, 684-691 (2008) |
 | Gene expression: Pioneering research
mTOR and S6 protein kinase-1 (S6K1) help assemble an efficient initiation complex during the first round of translation on newly spliced mRNAs.
Original research paper: Cell 133, 303-313 (2008) |
 | Cellular microbiology: Virus plays dead
Large particles such as the infectious, mature virus (MV) form of vaccinia may enter host cells undetected by employing apoptotic mimicry to stimulate macropinocytosis.
Original research paper: Science 320, 531-535 (2008) |
 | In brief: June 2008
DNA repair | Nuclear envelope | Mucosal immunology | Immune regulation | B-cell signalling | Metabolism | Angiogenesis | Evolution | Axon guidance | Excitotoxicity | Neurodegenerative disease | Synaptic plasticity | Pulmonary disorders | Anticancer drugs | Cell biology | Immunochemistry |
 | Cytokines: Keep your partner close
Interleukin-15 receptor alpha (IL-15Rα) presents IL-15 in trans to neighboring cells, and researchers have now shown that the IL-15–IL-15Rα complex is preassembled in dendritic cells following Toll-like receptor (TLR) stimulation.
Original research paper: J. Exp. Med. 205, 1213-1225 (2008) |
 | Cell polarity: APC throws the anchor
APC (adenomatous polyposis coli) anchors over 50 mRNAs — including Rab13 and Pkp4 (plakophilin 4) — to microtubule plus ends at the pseudopodial tips of migrating cells.
Original research paper: Nature 453, 115-119 (2008) |
 | Molecularly targeted therapy: JAK2 inhibitor restores balance in polycythaemia vera
A highly specific ATP-competitive Janus kinase 2 (JAK2) inhibitor shows promise for treating myeloproliferative disorders such as polycythemia vera, essential thrombocythemia and myelofibrosis.
Original research paper: Cancer Cell 13, 311-320 (2008) |
 | Cell signalling: Dynamic redistribution
Wnt5a signals through Rab4 and RhoB to control cell orientation, polarity and directional movement.
Original research paper: Science 320, 365-369 (2008) |
 | Autoimmunity: Type I interferon target revealed
Interferon-β (IFNβ) signaling in myeloid cells has a protective effect during autoimmune inflammation of the central nervous system.
Original research paper: Immunity 28, 675-686 ( 2008) |
 | Metastasis: Which way to the lungs?
TGFβ-mediated upregulation of the cytokine angiopoietin-like protein 4 (ANGPTL4) disrupts endothelial cell contacts, which contributes to lung metastasis of primary breast cancers.
Original research paper: Cell 133, 66-77 (2008) |
 | Synaptic transmission: Diffusion to speed up recovery
AMPARs (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors) recover from postsynaptic depression – receptor desensitization following stimulation – partly by lateral membrane diffusion and the exchange of desensitized receptors for 'fresh' ones.
Original research paper: Science 320, 201-205 (2008) |
 | Rewiring E. coli
By adding new connections between unrelated genes to a gene network, researchers can investigate network robustness and evolvability.
Original research paper: Nature 452, 840-845 (2008) |
 | DNA repair: Working on different ends
Whether double-stranded DNA breaks produce clean or 'ragged' overhanging ends affects the recruitment of checkpoint and repair proteins to the damaged sites in a cell-cycle-dependent manner.
Original research paper: Mol. Cell 30, 73-85 (2008) |
 | T-cell signalling: ITAMs: quantity over quality
A systematic analysis of the CD3 immunoreceptor tyrosine-based activation motifs (ITAMs), which transmit intracellular signals following T-cell receptor (TCR) ligation, illuminates the requirement for multiple ITAMs in T-cell development and function.
Original research paper: Nature Immunol. 9, 658-666 (2008) |
 | Metastasis: Trading in mitochondria
Exchanging the mitochondrial DNA (mtDNA) between mouse tumor cell lines has revealed mtDNA mutations that increase the metastatic potential of tumor cells by mediating the generation of reactive oxygen species (ROS).
Original research paper: Science 320, 661-664 (2008) |
 | Development: Extending the role of FGFs in the limb
Fibroblast growth factors (FGFs) are thought to specify distal fates along the proximal–distal axis in the mouse limb.
Original research paper: Nature 453, 401-405 (2008) |
 | Motionless fast 3D scanning
A 3D laser scanning microscopy method that requires no moving parts promises to expand the in vivo study of fast neuronal signaling at cellular and subcellular levels.
Original research paper: Nat. Neurosci., 11, 713-720 (2008) |
 | Cell signalling: A Rac1–JNK2–β-catenin domino cascade
Wnt signaling promotes Rac1-mediated activation of Jun N-terminal kinase-2 (JNK2), which phosphorylates β-catenin and promotes its nuclear translocation.
Original research paper: Cell 133, 340-353 (2008) |
 | T-cell responses: DCs get KITted out
Following exposure to allergens, dendritic cells stimulate a KIT–PI3K–interleukin-6 signaling pathway that promotes TH2- and TH17-cell responses.
Original research paper: Nature Med. 14, 565-573 (2008) |
 | Therapy: Reversed protection
CBLB502 — a toll-like receptor 5 (TLR5) agonist that induces NF-κB activation — inhibits apoptosis to protect hematopoietic and gastrointestinal tract cells from the radiation damage associated with radiotherapy.
Original research paper: Science 320, 226-230 (2008) |
 | Neurodegenerative disease: Inhibiting β-secretase where it matters
When β-secretase, the protein that produces the Alzheimer's-associated β-amyloid protein, was specifically inhibited at the lipid rafts of cell membranes it caused increased survival in a fly model of Alzheimer's disease and decreased β-amyloid production in a mouse model of the disease.
Original research paper: Science 320, 520-523 (2008) |
 | Immune evasion: Overcoming defensins
The Shigella flexneri bacterial pathogen lowers host defenses by modulating the expression of host antimicrobial defensin peptides.
Original research paper: J. Exp. Med. 205, 1121-1132 (2008) |
