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.
 | Angiogenesis: Tissue factor has a PAR-2 play
Independent of its function in coagulation, the TF-VIIa protease complex is now shown to induce angiogenesis through the activation of protease-activated receptor-2 signaling.
Original research paper: Nature Medicine 10, 502 – 509, (2004) |
 | Development: A joint movement
Fibronectin regulates epithelial organization during myocardial migration in zebrafish.
Original research paper: Dev. Cell 6, 371 – 382, (2004) |
 | In brief: May 2004
Cell migration | Development | Ubiquitylation | Apoptosis | Autoimmunity | Antigen Presentation | Oncogenesis | Oncogenesis | Neural development | Neural development | Chemical libraries |
 | Membrane trafficking: A new way to target
Two papers have highlighted a new way to target small GTPases to membranes.
Original research paper: Nature Cell Biol. 6, 405 – 413, (2004) |
 | Thymocyte development: Positive about calcineurin
Calcineurin is required for positive but not negative selection of developing T cells in the thymus.
Original research paper: Immunity 20, 255 – 266, (2004) |
 | Dendritic cells: IRF2 directs cell distinction
The transcription factor interferon regulatory factor 2 (IRF2) is crucial for the development of splenic and epidermal CD4+ dendritic cells.
Original research paper: Proc. Natl Acad. Sci. USA 101, 3909 – 3914, (2004) |
 | Oncogenesis: Staying active
Mechanism of activation of the RAS–ERK signaling pathway by oncogenic mutations of B–RAF.
Original research paper: Cell 116, 855 – 867, (2004) |
 | Therapeutics: Means to an end
Disruption of Akt signaling with the drug rapamycin reverses tumor chemoresistance in a mouse model of lymphoma.
Original research paper: Nature 428, 332 – 337, (2004) |
 | Synaptic plasticity: Spiny problems in MRX
Findings indicate that Ophn-1 normally maintains dendritic spine length by negatively regulating the RhoA/Rho-kinase signaling pathway.
Original research paper: Nature Neurosci. 7, 364 – 372, (2004) |
 | Whole organism screening: Zebrafish reduce drug discovery gridlock
A phenotype-based screen of a zebrafish model of aortic deformities has been used to identify pathways and potential drug leads that correct the disease.
Original research paper: Nature Biotechnol. 22, 595 – 599, (2004) |
 | TLR signaling: RIPping up NF-κB
RIP1 mediates Toll-like receptor 3-induced NF-κB activation downstream of the adaptor protein Trif.
Original research paper: Nature Immunology 5, 503 – 507, (2004) |
 | DNA replication: Sir2 finds its voice in replication
Researchers have identified a new role for the histone deacetylase Sir2 that is independent of its well—known roles in silencing–the negative regulation of the initiation of DNA replication in Saccharomyces cerevisiae.
Original research paper: Genes Dev. 18, 769 – 781, (2004) |
 | Cytokinesis: At a right angle
A new mechanism for coordinating spindle orientation and cell division in fission yeast has been proposed.
Original research paper: EMBO J. 23, 1289 – 1300, (2004) |
 | Innate immunity: Worms: the new Drosophila?
TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM.
Original research paper: Nature Immunol. 5, 488 – 494, (2004) |
 | Tumorigenesis: OutFOXing liver cancer
The Foxm1b transcription factor is essential for hepatocellular carcinoma development and can be inhibited by an Arf peptide.
Original research paper: Genes Dev. 18, 830 – 850, (2004) |
 | Targeted Therapies: Inhibiting aurora
An inhibitor of aurora-kinase activity causes arrest and apoptosis of cancer cells.
Original research paper: Nature Med. 10, 262 – 267, (2004) |
 | Targeted therapies: Bullseye
Insulin-like growth factor receptor-1 (IGF1R) inhibitors are selective and have significant antitumour activity.
Original research paper: Cancer Cell 5, 231 – 239, (2004) |
 | Neurobiology of addiction: The rewards of tPA
The tissue plasminogen activator—plasmin system participates in the rewarding effect of morphine by regulating dopamine release.
Original research paper: Proc. Natl Acad. Sci. USA 101, 3650 – 3655, (2004) |
 | GPCR signaling: Respiration provides inspiration for hypertension research
Two intermediates of the citric acid cycle, succinate and a-ketoglutarate, are ligands for the orphan receptors GPR91 and GPR99. Succinate-activated GPR91 increases hypertension through the renin-angiotensin system, thus providing a potential link between respiration and hemodynamic regulation.
Original research paper: Nature 429, 188 – 193, (13 May 2004) |
 | Cell migration: From stop to go
p27Kip1 modulates cell migration through regulation of RhoA activation.
Original research paper: Genes Dev. 18, 862 – 876, (2004) |
 | RNA interference: RISC assessment
Dcr-1 and Dcr-2 have distinct but overlapping roles in the siRNA and miRNA silencing pathways.
Original research paper: Cell 117, 69 – 81, (2004) |
 | Inflammation: Cytokine ignition complex characterized
NALP3 forms an IL-1ß-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder.
Original research paper: Immunity 20, 319 – 325, (2004) |
 | Tumour immunology: Preventing escape
Mouse melanoma cells express a T-cell inhibitor called galectin-1, which could be a useful therapeutic target.
Original research paper: Cancer Cell 5, 241 – 251, (2004) |
 | Therapeutics: Staying on target
Researchers describe a gene-therapy approach that specifically targets the endothelial cells of the growing tumor vasculature.
Original research paper: J. Clin. Invest. 113, 1017 – 1024, (2004) |
 | Innate immunity: PKR key to apoptosis
The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4.
Original research paper: Nature 428, 341 – 345, (2004) |
 | Transcriptional networks: A systems approach
The use of high-throughput data combined with a genome-scale computational model is aiding the elucidation of transcriptional regulatory and metabolic networks in E. coli.
Original research paper: Nature 429, 92 – 96, (06 May 2004) |
 | Cell cycle: The APC: a control freak?
The APC/C complex helps prevent the unscheduled degradation of SCFSKP2—CKS1 substrates during G1 phase and the consequent premature entry into S phase that could cause genetic instability.
Original research paper: Nature 428, 190 – 193, (2004) |
 | Mast Cells: Size does matter
The quantity and duration of FcRγ signals determine mast cell degranulation and survival.
Original research paper: Blood 103, 3093 – 3101, (2004) |
 | Tumorigenesis: Working backwards
EPHB4 promotes tumor angiogenesis by signaling through its membrane-bound ligand on endothelial cells.
Original research paper: Proc. Natl Acad. Sci. USA 101, 5583 – 5588, (2004) |
 | Glia: Myelin made to measure
The amount of neuregulin-1 that is produced by an axon tells Schwann cells how thick the myelin sheath around that axon should be.
Original research paper: Science 304, 700 – 703, (2004) |
 | Cardiovascular Disease: Plumbing for the heart
An experimental drug known as JTV519 enhances the binding of the protein calstabin–2 to a calcium channel present in heart cells, thereby stabilizing the channel in its closed state and preventing potentially dangerous calcium leakage.
Original research paper: Science 304, 292 – 296, (2004) |
