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.
 | Wound repair: Closure brings healing
Growth regulation of epithelial cells and wound repair is controlled by tight junctions segregating the growth factor heregulin on the apical membrane from its receptors on the basolateral membrane.
Original research paper: Nature 422, 322 – 326, (2003) |
 | DNA repair: Unpair to repair
Details of the exact role of ATM have been sketchy, but new data now sheds some light on how ATM is activated.
Original research paper: Nature 421, 499 – 506, (2003) |
 | In brief: March 2003
Regulatory Lymphocytes | Evolution | Checkpoints | Development |
 | Regulatory lymphocytes: Tolerance or immunity — DCs decide
v-rel reticuloendotheliosis viral oncogene homologue B (RELB), by controlling dendritic cell maturation and expression of CD40, could be important for determining the response of T cells to dendritic cells in lymphoid organs, resulting in either tolerance or immunity.
Original research paper: Immunity 18, 155 – 167, (2003) |
 | Regulatory lymphocytes: Direct DC hit activates TReg cells
Antigen presentation by immature dendritic cells in vivo can lead to the activation of TReg cells.
Original research paper: Blood 194, 769 – 779, (23 January 2003) |
 | Melanoma: Sunburn effects dissected
Components of the retinoblastoma (RB) pathway are important targets of ultraviolet-light-induced mutagenesis.
Original research paper: Proc. Natl Acad. Sci. USA 100, 1221 – 1225, (2003) |
 | Oncogenes: Decisions, decisions...
Loss of Notch1, along with upregulation of ß-catenin and Gli2, can promote a pro-proliferative, anti-differentiation state in skin cells.
Original research paper: Nature Genet. 33, 416 – 421, (2003) |
 | Oncogenesis: Switching off death
Jun promotes tumorigenesis by switching off p53, which, in turn, switches off death.
Original research paper: Cell 112, 181 – 192, (2003) |
 | Cancer: Parc keeper
Parc (p53-associated, parkin-like cytoplasmic protein) anchors p53 in the cytoplasm and prevents the tumor suppressor from entering the nucleus.
Original research paper: Cell 112, 29 – 40, (2003) |
 | RNA-targeted drugs: The ESSENCE of correction
ESSENCE (exon-specific silencing enhancement by small chimeric effectors) can correct genetic typos by emulating the function of essential splicing factors called serine/arginine-rich proteins.
Original research paper: Nature Struct. Biol. 10, 120 – 125, (2003) |
 | Src-family protein tyrosine kinases: Had to B
Src-family protein tyrosine kinases play an essential role in the activation of NF-?B during the development of B cells through a pathway separate from that of the tyrosine kinase Syk.
Original research paper: Nature Immunology 4, 274 – 279, (2003) |
 | Lipid rafts: A deadly gang
Lipid rafts have a potential importance as therapeutic targets for drugs against anthrax.
Original research paper: J. Cell Biol. 160, 321 – 328, (2003) |
 | Mitochondrial Biogenesis: NO energy
NO's role in mitochondrial biogenesis has now been studied, and the results may be of help in the treatment and prevention of metabolic syndrome.
Original research paper: Science 299, 896 – 899, (2003) |
 | T-cell development: The right niche for Notch?
Notch1 signalling has a role in an intrathymic mechanism of T-cell commitment.
Original research paper: J. Immunol. 170, 1299 – 1303, (2003) |
 | Tumour suppressors: Keep cancer on the run
Cyclic nucleotide gated channels regulate cell proliferation.
Original research paper: Proc. Natl Acad. Sci. USA (10 Feb 2003) |
 | Neurological disorders: Caspase, the friendly protein
Experiments point towards a potential mechanism for a neuroprotective effect known as preconditioning that relies on limited activation of caspase 3 to induce subsequent neuroprotection.
Original research paper: Proc. Natl Acad. Sci. USA 100, 715 – 720, (2003) |
 | Apoptosis: If I had a hammer...
An apoptosis-promoting compound has been identified by high-throughput screening, revealing the distinct roles of two proteins, both with links to cancer, in the progression of cell death.
Original research paper: Science 299, 223 – 226, (2003) |
 | Hedgehog signaling: Small-cell lung cancer shows its spikes
The hedgehog (Hh) signaling pathway is activated during the repair of acute airway injury and lung development. A subset of small-cell lung cancers (SCLC) also exhibits Hh pathway activation, which is required for the maintenance of the malignant phenotype. Thus, SCLC may recapitulate a Hh regulated stage of airway epithelial differentiation and may respond to pharmacological blockade of the Hh pathway.
Original research paper: Nature 422, 313 – 317, (2003) |
 | Apoptosis: Double trouble
p53, by moving rapidly to the mitochondria, effectively 'jump starts' and amplifies its slower-starting transcription-dependent effect on apoptosis.
Original research paper: Molecular Cell (27 January 2003) |
 | Polarity: Two become one
The pathways Cdc42–Par6–protein kinase C? (PKC?), and glycogen synthase kinase-3ß (GSK-3ß)–ß-catenin–adenomatous polyposis coli (Apc) may together be a single mechanism to spatially control cell polarity.
Original research paper: Nature 421, 753 – 756, (2003) |
 | Innate immunity:
Double protection
Not only does the chemokine CCL28 attract antibody-secreting cells, but it also has the unexpected capacity to kill microorganisms directly.
Original research paper: J. Immunol. 170, 1452 – 1461, (2003) |
 | Autoimmunity: Cell death in diabetes
Fas-mediated apoptosis of ß-cells has an important role in diabetes. New results validate the development of therapeutic strategies to target death-receptor signaling.
Original research paper: Proc. Natl Acad. Sci. USA 100, 628 – 632, (2003) |
 | Genomic instability: Dangerous division
Cancer cells might use amplification of AURORA-A as a mechanism for deregulating the checkpoint.
Original research paper: Cancer Cell 3, 51 – 62, (2003) |
 | Axon growth: Fas track to recovery
The regeneration of axons after peripheral nerve injury depends on the activation of signaling pathways that induce neurite sprouting from the damaged neurons. Research now shows that a pivotal component of one such pathway is the Fas receptor.
Original research paper: Nature Cell Biol. 5, 118 – 125, (2003) |
 | Cytoskeletal remodeling: The Rho-le of Rac
Rac regulates cytoskeletal remodeling via inhibition of Rho GTPase activity in a redox-dependent manner.
Original research paper: Nature Cell Biology 5, 236 – 241, (2003) |
 | Apoptosis: Follow the fly path
Parallels have now been drawn between the way that flies and mammals induce p53-dependent cell death.
Original research paper: Genes Dev 17, 359 – 367, (2003) |
 | Tumorigenesis: Getting under the skin
New data highlight the problems of targeting NF-?B as a method of increasing apoptosis in tumors — use of such agents, which are in development, could actually promote tumorigenesis in the skin.
Original research paper: Nature 421, 639 – 643, (2003) |
 | Ion channels:
Charging at the gate
Evidence suggests that specific electrostatic interactions between residues of the extracellular domain and the linker between two transmembrane domains are crucial for gating of the GABAA (?-aminobutyric acid) receptor channel.
Original research paper: Nature 421, 272 – 275, (2003) |
 | Inflammation: Targeting two for the price of one
Inhibiting two enzymes in the inflammatory cascade with a single engineered peptide dramatically reduces inflammation in animal models of inflammation.
Original research paper: J. Clin. Invest. 111, 121 – 128, (2003) |
 | Structure-based drug design: Can GPCR models work?
Research now shows that models of a range of G-protein-coupled receptors based on the rhodopsin structure can be successfully used to identify both antagonists and agonists by virtual screening of compound libraries.
Original research paper: Proteins 50, 5 – 25, (2003) |
