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.
 | Inflammation: Sneezing at the right PI(3)K
The p110δ isoform of PI(3)K is a key regulator of mast cell homeostasis and the allergic response.
Original research paper: Nature 431, 1007 – 1011, (21 October 2004) |
 | Cell polarity: Territorial proteins
Atypical protein kinase C (aPKC) acts upstream of Par1 to maintain appropriate assymetric membrane domains and establish apicobasal polarity in epithelial cells.
Original research paper: Curr. Biol. 14, 1425 – 1435, (2004) |
 | In brief: October 2004
Proteomics | Nucleocytoplasmic transport | Cytokinesis | T-cell responses | Natural killer T cells | Cytokines | B-cell signalling | Breast Cancer | Therapeutics | High-throughput screening | Biotechnology |
 | Regulating 'stickiness': A key role for RAPL
RAPL (regulator of cell adhesion and polarization enriched in lymphoid tissues), an effector molecule for the GTPase Rap1, is a key regulator of chemokine-triggered cell adhesion and integrin-mediated migration.
Original research paper: Nature Immunol. 5, 1045 – 1051, (2004) |
 | MKP5: Modifying kinase-regulated pathways
MAP kinase phosphatase 5 (MKP5) is required for T-cell proliferation and is a negative regulator of effector T-cell cytokine production.
Original research paper: Nature 430, 793 – 797, (2004) |
 | Genetics: Extra extra
A unique fusion between NUP214 and ABL1 has been identified, which occurs only on episomes in human T-cell acute lymphoblastic leukaemia (T-ALL) cells.
Original research paper: Nature Genet. 36, 1084 – 1089, (2004) |
 | Developmental biology: Testing times for Hedgehog
Hedgehog signaling depends on the ratio of bound to unbound Patched (Ptc) and both spatial and temporal gradients of morphogen are important in specifying digit identity in the forelimb.
Original research paper: Nature 431, 76 – 80, (2004) |
 | Psychiatric disorders: The anxious transmitter
Neuropeptide S (NPS) binds to the G-protein coupled receptor NPSR and participates in a neurotransmitter system that modulates sleep-wake cycles and anxiety.
Original research paper: Neuron 43, 487 – 497, (2004) |
 | Pharmacogenomics: ABCs of drug resistance
A new database on all human ABC transporters in cancer cells provides information on their expression patterns coupled to the sensitivity of the cells to various anticancer drugs.
Original research paper: Cancer Cell 6, 129 – 137, (2004) |
 | Tumor metastasis: Waiting for Snail
The transcription factor Snail, an important regulator of epithelial-mesenchymal transition, has now been shown to be dually controlled by the activity of GSK3ß.
Original research paper: Nature Cell Biology 6, 931 – 940, (2004) |
 | Cell cycle: Split timing
The timing of central-spindle assembly, and hence cell division, is controlled by fine-tuning the activities of cell-cycle kinases and phosphatases.
Original research paper: Nature 430, 908 – 913, (2004) |
 | Membrane fusion: Taking steps to unite
Inner- and outer-membrane fusion in mitochondria are two distinct events, but both require the activity of the outer membrane protein Fzo1.
Original research paper: Science 305, 1747 – 1752, (2004) |
 | Dendritic cells: Guess who
Dendritic cells recruited to ovarian cancers by ß-defensins can contribute to vasculogenesis under the influence of VEGF.
Original research paper: Nature Med. 10, 950 – 958, (2004) |
 | HIV: Driving HIV out of hiding
New genes have been identified that can drive HIV out of latency and into lytic replication; implications for antiretroviral drugs.
Original research paper: J. Virol. 78, 9458 – 9473, (2004) |
 | Tumorigenesis: Two faces of hypoxia
Hypoxia and defective apoptosis drive cancer progression by promoting genomic instability.
Original research paper: Genes Dev. 18, 2095 – 2107, (2004) |
 | Gene regulation: A code of transcriptional behaviour
A new map has been created that details how yeast transcription factors interact to transcribe the genome.
Original research paper: Nature 431, 99 – 104, (2004) |
 | Chemistry: Stabilizing staples
Modifying the Bcl2 pathway in apoptosis by using hydrocarbon staples provides both an attractive anti-cancer strategy and a tool for modulating protein interactions.
Original research paper: Science 305, 1466 – 1470, (2004) |
 | Proteomics: Getting a handle on protein farnesylation
A new 'tagging-via-substrate' technique has enabled the broad identification of cellular targets of protein farnesylation.
Original research paper: Proc. Natl. Acad. Sci. USA 101, 12479 – 12484, (2004) |
 | Genomics: SAGE takes a look at the 5' end
Adapting the method for long serial analysis of gene expression has led to the identification of the 5' ends of new genes.
Original research paper: Nat. Biotechnol. 22, 1146 – 1149, (2004) |
 | Dopamine signaling: A question of choice
Dopamine signals through two antagonistic G-protein coupled receptor pathways to control locomotion in the nematode.
Original research paper: Nature Neuroscience 7, 1096 – 1103, (2004) |
 | Autophagy: Breakdown recovery
Autophagy, a process by which cells recover essential nutrients in response to starvation, is regulated by components of both the TOR and PI3K signaling pathways.
Original research paper: Dev. Cell 7, 167 – 178, (2004) |
 | Dendritic cells: Remodelling by TLRs
In response to innate immune stimuli, dendritic cells upregulate antigen uptake through rapid remodeling of the actin cytoskeleton.
Original research paper: Science 305, 1153 – 1157, (2004) |
 | Immunoregulation: Mediating endotoxin tolerance
New role for the phosphatase SHIP in the regulation of endotoxin tolerance.
Original research paper: Immunity 21, 227 – 239, (2004) |
 | Tumorigenesis: Dependence on independence
Netrin-1 controls colorectal tumorigenesis by regulating DCC-induced apoptosis.
Original research paper: Nature 431, 80 – 84, (2004) |
 | Tumorigenesis: Inflammatory debate
The transcription factor NF-κB contributes to tumorigenesis by suppressing apoptosis and increasing cell proliferation in response to inflammatory cytokines.
Original research paper: Cell 118, 285 – 296, (2004) |
 | RNA silencing: Small RNAs take the tube
Plants can mount a systemic response to viral infection by transporting siRNAs over long distances in the network of phloem tubes.
Original research paper: Plant Cell 16, 1979 – 2000, (2004) |
 | Gliogenesis: Oligodendrocytes don't need ID
The inhibitory effects of BMP4 on oligodendrocyte differentiation are mediated through interactions between ID and OLIG proteins.
Original research paper: Development 131, 4131 – 4142, (2004) |
 | TLR signaling: Putting a stop to it
The deubiquitinating enzyme A20 is now shown to terminate Toll-like receptor (TLR) signaling by modulating NF-κB activity.
Original research paper: Nature Immunology 5, 1052 – 1060, (2004) |
 | Telomeres: Extreme protection
The telomere binding protein TRF2 protects chromosome ends by directly inhibiting activation of the ATM kinase.
Original research paper: PLoS Biology 2, 1150 – 1156, (2004) |
 | Signal transduction: Take it away...
The secreted protein Argos functions as an antagonist of EGFR signaling by sequestering the EGF ligand Spitz.
Original research paper: Nature 430, 1040 – 1044, (2004) |
 | Immune tolerance: Staying calm under provocation
The E3 ubiquitin ligase, Cbl-b, has a new role; that of being an important player during T-cell anergy induction.
Original research paper: Immunity 21, 167 – 177, (2004) |
 | Immunology: Deregulation required?
Inhibiting regulatory T cell activation or migration could improve the efficacy of the antitumor response.
Original research paper: Nature Med. 10, 942 – 949, (2004) |
 | Oncogenes: Keeping track of stats
STAT3 is responsible for maintaining the proliferation and survival of cancer cells in skin tumorigenesis.
Original research paper: J. Clin. Invest. 114, 720 – 728, (2004) |
 | Synaptic plasticity: Found in translation
BDNF regulates the local translation of a select group of mRNAs at the synapse, by a mechanism that involves the mTOR-PI3K signaling pathway.
Original research paper: J. Neurosci. 24, 7366 – 7377, (2004) |
 | Apoptosis: Bid for death
A novel multidisciplinary NMR-based approach provides a powerful tool for the rational design of small molecules that bind and antagonize the pro-apoptotic molecule Bid.
Original research paper: Chem. Biol. 11, 1107 – 1117, (2004) |
 | Cellular microbiology: Ping-pong cell-fate control
New findings in the bacterium Caulobacter cresentus suggest that cytokinesis is a trigger for cell development; important implications for higher organisms.
Original research paper: Cell 118, 579 – 590, (2004) |
 | Immunological synapses: Directing cell fate
T cell receptor and cytokine receptor co-polarization at immunological synapses influences naive T cell fate.
Original research paper: Nature 431, 527 – 532, (30 September 2004) |
 | Apoptosis: Managing stress
Bax inhibitor-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress.
Original research paper: Mol. Cell 15, 355 – 366, (2004) |
 | Immune evasion: Signal disruption enables escape
Herpesvirus saimiri uses tyrosine kinase-interacting protein to inhibit the activation of ZAP70, thereby disrupting the subsequent T-cell signaling cascades required for T-cell activation.
Original research paper: J. Exp. Med. 200, 681 – 687, (2004) |
 | Lung cancer: Smoking out differences
Differences in the genetic make-up of tumors from smokers and non-smokers mean that those that arise in smokers are less likely to respond to existing targeted therapies.
Original research paper: Proc. Natl Acad. Sci. USA 101, 13306 – 13311, (2004) |
 | Obesity: Tipping the energy balance
By creating two mouse mutants that do not gain weight, two groups report progress towards producing an anti-obesity wonder drug.
Original research paper: Genes Dev. 18, 1970 – 1975, (2004) |
 | Glia: Waves of proliferation
A novel mechanism has been discovered whereby the proliferation of radial glial cells in the cortical ventricular zone (VZ) during development is regulated by spontaneous waves of calcium.
Original research paper: Neuron 43, 647 – 661, (2004) |
 | Chemistry: Chemical engineering in vivo
Metabolic oligosaccharide engineering incorporates unnatural sugars into cell-surface glycans, and has been previously demonstrated in vitro; now this technique can also be used in vivo.
Original research paper: Nature 430, 873 – 877, (2004) |
