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.
 | Immune response: TRAF-icking signals from Toll-like receptors
A TNF-associated factor 3 (TRAF3)-dependent pathway regulates interleukin-10 (IL-10) and interferon (IFN) production to direct the outcome of Toll-like receptor (TLR) signaling.
Original research paper: Nature (2005) |
 | Innate immunity:
VAMPing up macrophage responses
A joint trafficking pathway that links proinflammatory cytokine secretion and phagocytosis of pathogens has been identified in macrophages.
Original research paper: Science (10 Nov 2005) |
 | In brief: December 2005
Metabolism | Endocytosis | Cytokines | Targeted therapies | Prognostic markers | Cellular adhesion | Human disease | Mouse models | RNA world | Computational biology | Ion channels | Neurodegeneration | Cardiotoxicity | Infectious diseases | Imaging and visualization | Molecular libraries | Cell biology |
 | Multi-purpose mutations
Specific mutations in epidermal growth factor receptor (EFGR) that have been linked to the acquisition of resistance to tyrosine kinase inhibitor drugs, can also determine genetic susceptibility to bronchoalveolar lung cancer.
Original research paper: J. Clin. Oncol. 23, 8081 – 8092, (2005) |
 | Silent science
Epigenetic silencing of the transcriptional repressor hypermethylated in cancer 1 (HIC1) directly increases the expression of the histone deacetylase SIRT, and prevents an efficient p53-mediated response to DNA damage.
Original research paper: Cell 123, 437 – 448, (2005) |
 | Gene expression: Something for a stressful day
Stress can trigger the release of an mRNA that is normally retained in the nucleus to the cytoplasm and its subsequent translation into protein.
Original research paper: Cell 123, 249 – 263, (2005) |
 | Silencing neurodegeneration
siRNA mediated knock-down of the proteolytic enzyme β-secretase (BACE1) ameliorates Alzheimer disease neuropathology in a transgenic mouse model.
Original research paper: Nature Neurosci. 8, 1343 – 1349, (2005) |
 | Computational chemistry: Ready, steady, screen!
A unique competition in which entrants were challenged to computationally predict the results of a high-throughput screen shows that inhibitors are particularly difficult to predict.
Original research paper: J. Biomol. Screen. 10, 653 – 657, (2005) |
 | MicroRNA: the perfect host
By creating an expression cassette that inserts a short hairpin RNA within a ubiquitous microRNA, scientists can now achieve highly efficient target gene knockdown.
Original research paper: Nat. Genet. 37, 1289 – 1295, (2005) |
 | Developmental biology: Hedgehog signaling deconstructed
New regulators of Hedgehog signaling are identified in a genome wide RNA interference screen in Drosophila.
Original research paper: Nature Genetics 37, 1323 – 1332, (2005) |
 | B cells: Phosphorylation initiates AID response
A new study shows that cyclic-AMP-dependent protein kinase (PKA) regulates antibody diversification by phosphorylating activation-induced cytidine deaminase (AID).
Original research paper: Nature 438, 508 – 511, (2005) |
 | Immune responses: Shuttling serotonin: not just in our heads
Serotonin might be delivered from dendritic cells to T cells across the immunological synapse in a manner similar to that which occurs between neurons.
Original research paper: Blood (13 Oct 2005) |
 | Metastasis: Easing the pain
An antibody which blocks nerve growth factor (NGF) attenuates bone pain in a mouse model of prostate bone cancer.
Original research paper: Cancer Res. 65, 9426 – 9435, (2005) |
 | Gene expression: Which mean do you mean?
Gene-expression levels between individual cells are distributed log-normally implying that the geometric mean may be a more appropriate way to represent the data than the more commonly quoted arithmetic mean.
Original research paper: Genome Res. 15, 1388 – 1392, (2005) |
 | Neurophysiology: The moody barrier
Moody, a gene that encodes a newly identified G-protein-coupled receptor (GPCR), is necessary for the formation and maintenance of the fly blood-brain barrier.
Original research paper: Cell 123, 133 – 144, (2005) |
 | Inflammatory disease: Local therapy for inflammatory bowel disease
Local or systemic delivery of nuclear factor-κB (NF-κB) decoy oligodeoxynucleotides have been used to successfully treat inflammatory bowel disease in two mouse models.
Original research paper: J. Clin. Invest. 115, 3057 – 3071, (2005) |
 | Bacterial physiology: Signal interference
Bacteria can interfere with the ability of competing species to assess and respond correctly to changes in cell population density by manipulating autoinducer 2 (AI-2) signaling.
Original research paper: Nature 437, 750 – 753, (2005) |
 | β-arrestins: Notching up regulation
Kurtz (krz), a non-visual β-arrestin, acts in concert with Deltex (dx) to attenuate Notch signaling via ubiquitination-dependent degradation of the Notch receptor.
Original research paper: Nature Cell Biology 7, 1191 – 1201, (2005) |
 | Fertility: Food for life
The metabolic regulation of oocyte apoptosis is linked to the calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated regulation of caspase-2.
Original research paper: Cell 123, 89 – 103, (2005) |
 | Phagocytosis: ER fails to make a contribution
Contrary to previous reports, a new study shows that the endoplasmic reticulum (ER) does not contribute membrane to the phagosome.
Original research paper: Cell 123, 157 – 170, (2005) |
 | Tumor Suppressors: Look both ways
The Krüppel-like factor 4 (KLF4) transcription factor can act as an oncogene by repressing p53, but can also induce cell-cycle arrest by increasing the expression of the cyclin-dependent-kinase inhibitor p21.
Original research paper: Nature Cell Biol. 7, 1074 – 1082, (2005) |
 | Systems biology: Linked-up loops: a reliable means of control
A computational modeling study shows that the optimal output of a signaling pathway is obtained when both fast and slow positive feedback loops are combined.
Original research paper: Science 310, 496 – 498, (2005) |
 | Neurodegenerative disorders: The lipid connection
It has been found that amyloid precursor protein (APP) processing affects both cholesterol and sphingomyelin metabolism, thus shedding light on the link between lipids and Alzheimer's disease.
Original research paper: Nature Cell Biol. 7, 1118 – 1123, (2005) |
 | Regeneration: A new stop signal
Epidermal growth factor receptor (EGFR) activation mediates myelin-induced inhibition of axonal regeneration.
Original research paper: Science 310, 106 – 110, (2005) |
 | Cell Biology: Teaching cell biologists how to count
A new method to quantify the fluorescence of fusion proteins in cells allows researchers to determine global and local concentrations of proteins.
Original research paper: Science 310, 310 – 314, (2005) |
 | Yeast kinome: global network emerges
A screen using protein chip technology identifies substrates for most protein kinases in yeast; over 4,000 phosphorylation events on 1,325 subtrates are assembled into the first global phosphorylation map for yeast.
Original research paper: Nature 438, 679 – 684, (2005) |
 | Web watch: Towards a human protein atlas
A new database containing thousands of images of protein expression in human tissue allows users to systematically explore the human proteome. |
 | Immune regulation: Take two for Notch
Notch signaling is not only required for T cell differentiation but also for the generation of a protective TH2-cell response in vivo.
Original research paper: J. Exp. Med. 202, 1037 – 1042, (2005) |
 | Metabolism: Excess energy
Inhibition of ATP citrate lyase (ACL), a key enzyme linking glucose metabolism to lipid synthesis, limits tumor cell proliferation and survival.
Original research paper: Cancer Cell 8, 311 – 321, (2005) |
 | Cancer epigenetics: Dangerous unmarked genes
A loss of imprinting predisposes cells to tumorigenesis by lowering the threshold for transformation.
Original research paper: Cancer Cell 8, 275 – 285, (2005) |
 | From kiss-and-run to crosstalk
Two studies examine the mechanisms of astrocytic transmitter release and its role in regulating synaptic strength and plasticity.
Original research paper: J. Neurosci. 25, 9236 – 9243, (2005) |
 | Antibacterial Drugs: Peptide power
Small peptides with potent antimicrobial activity against Gram-positive bacteria herald a new class of antibiotics.
Original research paper: Nature Med. 11, 1082 – 1087, (2005) |
 | Viral infection: Neurons fight back
A new study shows that human neurons, in absence of glia, have the intrinsic machinery to sense virus infection.
Original research paper: J. Virol. 79, 12893 – 12904, (2005) |
