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.
 | GPCR signaling: Receptive to Activation
Opioid receptor random mutagenesis has revealed a three-step model for G protein-coupled receptor activation.
Original research paper: Nature Structural Biology 10, 629 – 636, (2003) |
 | DNA repair:
Sensing breakdown
A 'common intermediate' for DNA damage and replication problems has been identified, that can be 'sensed' by the ATM- and Rad3-related (ATR)-dependent checkpoint.
Original research paper: Science 300, 1542 – 1548, (2003) |
 | In brief: August 2003
Cytokinesis | Ubiquitylation | Signaling | Technique | Synaptic physiology | Development | Ion channels | Anticancer Drugs |
 | Immune evasion: The disarming effects of anthrax
The complex known as lethal toxin disrupts the MAPK intracellular signaling pathway in dendritic cells by cleaving mitogen or extracellular signal regulated kinase kinases (MEKs).
Original research paper: Nature 424, 329 – 334, (2003) |
 | DCs: The immune system's flexible friend
Results show that non-plasmacytoid dendritic cells can produce type I IFNs during infection with virus, and a Toll-like receptor-independent pathway exists for the activation of dendritic cells.
Original research paper: Nature 987, 180 – 187, (2003) |
 | Therapeutics:
How degrading!
Bortezomib – the first small-molecule inhibitor of proteasome activity to be tested in clinical trials – is effective in treating patients with refractory myeloma.
Original research paper: N. Engl. J. Med. 348, 2609 – 2617, (2003) |
 | Oncogenes:
Who's doing the dirty work for MYC?
The human Werner syndrome gene, WRN, is a direct target of MYC, and MYC-driven WRN upregulation prevents cellular senescence and consequently leads to tumorigenesis.
Original research paper: Genes Dev. 17, 1569 – 1574, (2003) |
 | Gene expression: Clockwork conductor
Drosophila Clock can generate ectopic circadian clocks.
Original research paper: Cell 113, 755 – 766, (2003) |
 | Evolution: A tangled web
Research indicates that the Notch/Delta signaling pathway was involved in segmentation in the ancestors of insects.
Original research paper: Nature 423, 863 – 865, (2003) |
 | G-protein-coupled receptors: RGS puts the brakes on
Two papers give new insight into regulators of G-protein signaling (RGS) proteins.
Original research paper: Neuron 38, 857 – 862, (2003) |
 | Lymphocyte adhesion: all Rap'ped up
RAPL is a Rap-1 effector molecule involved in relaying 'inside-out' signals to integrins in order to regulate lymphocyte activation and adhesion.
Original research paper: Nature Immunology 4, 741 – 748, (2003) |
 | Signalling: Avoiding shade
In plants, the phyB/PFT1/FT pathway may be a photoperiod-independent light-quality sensing pathway that triggers flowering in response to a low ratio of red to far-red incoming light.
Original research paper: Nature 423, 881 – 885, (2003) |
 | Vaccines:
Shoot but don't kill
Co-administration of antigen-encoding DNA with DNA that encodes the anti-apoptotic molecule BCL-XL by gene-gun delivery to the skin can enhance T-cell responses to the antigen.
Original research paper: J. Clin. Invest. 112, 109 – 117, (2003) |
 | Telomerase: Pathways to telomerase activation
At least three pathways — TGF-ß, MAD1 and menin — all of which are involved in human cancer, regulate expression of telomerase.
Original research paper: Cell 113, 881 – 889, (2003) |
 | Diabetes:
Connectin' through adiponectin
The cloning of adiponectin receptors should aid in unraveling the mechanisms by which adiponectin acts, and the design and development of new antidiabetes therapies.
Original research paper: Nature 423, 762 – 769, (2003) |
 | Macrophages: Another dimension for TIR signaling
An MyD88-independent Toll-like receptor signaling pathway operates in macrophages via the adaptor protein Trif to produce interferon-ß and contributes to the production of inflammatory proteins.
Original research paper: Nature 424, 743 – 748, (2003) |
 | P53:
A stabilizing influence
A newly identified interaction between the ribosomal protein L11 and a negative regulator of p53, HDM2, could represent a stress-induced pathway for p53 stabilization.
Original research paper: Cancer Cell 3, 577 – 587, (2003) |
 | Apoptosis:
I will survive
Differential regulation of Raf by basic fibroblast growth factor and vascular endothelial growth factor protects endothelial cells from intrinsic- and extrinsic-mediated apoptosis, respectively.
Original research paper: Science 301, 94 – 96, (2003) |
 | Antigen presentation:
Dressing up
Toll-like receptor 2 internalizes antigen for presentation to CD4+T cells and could therefore be an efficient vaccine target.
Original research paper: J. Immunol. 171, 32 – 36, (2003) |
 | Phagocytosis:
Come and get it!
Apoptotic cells can induce migration of phagocytes via a caspase-3-mediated release of a lipid attraction signal.
Original research paper: Cell 113, 717 – 730, (2003) |
 | Fresh from the pipeline:
Gefitinib
Original research paper: Eur. J. Cancer 37, S4 – S66, (2001) |
 | Antifungals:
Doing the two step
Antifungal activity of the sodium-channel blocker amiodarone is mediated by the disruption of calcium homeostasis.
Original research paper: J. Biol. Chem. 300, 195 – 199, (2003 May 16) |
 | Endothelin-B receptor: The painless pathway
A new peripheral opioid analgesic pathway involving endothelin-1 and its G protein-coupled receptor ETB has been characterized, providing potential novel targets for the treatment of acute pain.
Original research paper: Nature Medicine 9, 1055 – 1061, (2003) |
 | Cardiac Disease:
When exercise is deadly
A 'leaky' Ca2+-release channel is mutated in catecholaminergic polymorphic ventricular tachycardia patients and may be responsible for triggering fatal arrhythmias.
Original research paper: Cell 113, 829 – 840, (2003) |
 | Lymphocyte Signalling:
Contrasting genetic approaches find a role for CARD11
A member of the membrane-associated guanylate kinase family of proteins known as CARD11 or CARMA1 is essential for lymphocyte activation.
Original research paper: Immunity 18, 751 – 762, (2003) |
 | Metastasis:
Chain-store cancer
RAF kinase inhibitor protein (RKIP) suppresses prostate cancer metastasis.
Original research paper: J. Natl Cancer Inst. 95, 878 – 889, (2003) |
 | Cell biology of the neuron:
The travels of neuregulin
New data make a compelling case for neuregulin-1-mediated intracellular signaling.
Original research paper: J. Cell Biol. 161, 1133 – 1141, (2003) |
 | p53: Interferon with cancer
A previously unrecognised link has been established between interferon signaling and p53 in tumor suppression and antiviral immunity.
Original research paper: Nature 424, 516 – 523, (2003) |
 | Stem cells: Hidden talents
Targeting Wnt signaling might be effective in treating neuromuscular degenerative disease, as muscle-derived CD45+ stem cells can respond to Wnt signaling by becoming muscle cells.
Original research paper: Cell 113, 841 – 852, (2003) |
 | SOCS3: A new target for anti-allergy drugs
SOCS3, which is mainly expressed by TH2 cells, regulates the onset and maintenance of TH2-cell-mediated allergic responses.
Original research paper: Nature Med. 6, 410 – 416, (2003) |
 | Therapeutic targets: TORpedoing cancer cells
Rapamycin-induced apoptosis is caused by prolonged activation of the JNK signaling pathway, but only in cells that lack functional p53.
Original research paper: Mol. Cell 11, 1491 – 1501, (2003) |
 | Sensory systems: Chemokines inflame the pain
Researchers now highlight an important role for G-protein-coupled chemokine receptors in the processing of chronic pain signals.
Original research paper: Proc. Natl Acad Sci. USA 100, 7947 – 7952, (2003) |
 | Lead discovery: Guided by nature
Natural inhibitors of particular proteins can be good starting points for the discovery of inhibitors of structurally related proteins.
Original research paper: J. Med. Chem. 41, 2878 – 2890, (2003 Jun 5) |
