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.
 | DNA repair: ATMachine
Significant headway has been made in our understanding of the Ataxia-telangiectasia mutated (ATM) activation mechanism. After exposure to ionizing radiation, ATM is rapidly phosphorylated at a single residue, Ser 1981, in an amino-terminal domain conserved among PI(3)Ks.
Original research paper: Nature 421, 499 – 506, (2003) |
 | Cell cycle:
Endless cycling
Tsai and McKay now report in Genes & Development a nucleolar mechanism involving nucleostemin and p53 that regulates cell-cycle progression in stem cells and cancer cells.
Original research paper: Genes Dev. 16, 2991 – 3003, (2002) |
 | In brief: January 2003: Part 1
Development | Lymphoid organogenesis | Signalling | Checkpoints | Neurotrophic Factors | Gene Therapy |
 | In brief: January 2003: Part 2
Cell cycle | Signal transduction | Natural killer cells | Oncogenes | Therapeutics | Stem Cells | Lead Identification |
 | Parasite immunity: Why worms are a turn off
Chistosome lyso-phosphatidylserine seems to signal through TLR2 to direct the induction of IL-10-secreting helper T cells, possibly accounting for the skewing to IL-10 production and T-cell hyporesposiveness that is seen during chronic schistosomiasis.
Original research paper: J. Biol. Chem. 277, 48122 – 48129, (2002) |
 | Translocations: Rare simplicity
Tognon et al. now report a translocation event — between the ETV6 transcription factor on chromosome 12 and the protein tyrosine kinase domain of the neurotrophin-3 receptor NTRK3 on chromosome 15 — that forms a dominantly acting oncogene and causes a rare form of breast cancer.
Original research paper: Cancer Cell 2, 367 – 376, (2002) |
 | Ion channels: How the channel lost its symmetry
Two recent studies provide evidence that rod cyclic nucleotide-gated channels have three A1 and one B1 monomers.
Original research paper: Neuron 36, 881 – 889, (2002) |
 | Inflammation regulation: The role of nicotinic Ach receptor a7
The nicotinic acetylcholine receptor a7 is responsible for the inhibition of macrophage TNF release via the parasympathetic anti–inflammatory pathway, thus opening up new avenues for the design of experimental anti–inflammatory therapeutics.
Original research paper: Nature 421, 384 – 388, (2003) |
 | Inflammation: A combined effort
The proteinase matrilysin (also known as matrix metalloproteinase 7), the proteoglycan syndecan 1 and the chemokine KC act in concert to direct inflammatory cells to sites of injury in the lung.
Original research paper: Cell 111, 635 – 646, (2002) |
 | Immune regulation: Balancing act
A study in Nature shows that regulatory T (TReg) cells at the site of chronic infection might be crucial for parasite persistence and long-lasting immunity.
Original research paper: Nature 420, 502 – 507, (2002) |
 | Tumour suppressors: The stabilizing influence of VHL
Reporting in Nature Cell Biology, Krek and colleagues have uncovered a novel function for VHL — microtubule stabilization — and show that disruption of this function is linked to the development of a specific subtype of von Hippel–Lindau disease.
Original research paper: Nature Cell Biology 4, 64 – 70, (2003) |
 | Neurulation: The long and the short of it
The authors who previously showed that the signal transduction molecule Dishevelled is required both for convergent extension and neural tube closure now clarify the relationship between these two events.
Original research paper: Development 129, 5815 – 5825, (2002) |
 | Synaptic plasticity: The plasticity of chromatin
When Aplysia neurons receive opposing signals at different synapses, long-term depression predominates over long-term facilitation.
Original research paper: Cell 111, 483 – 493, (2002) |
 | NSAIDS: Better design through chemistry
The structural requirements for the induction of apoptosis are distinct from those that mediate COX2 inhibition.
Original research paper: J. Natl Cancer Inst. 94, 1745 – 1757, (2002) |
 | Chemokine receptor Cxcr4: Putting germ cells on the right path
Nüsslein-Volhard and colleagues have revealed a role for G-protein-coupled receptors in embryonic development by identifying a chemokine receptor and its ligand that guide migratory germ cells in zebrafish.
Original research paper: Nature 421, 279 – 282, (2003) |
 | Protein translocation: Crossing the divide
The TIM23 complex translocates presequence-containing proteins across, or into, the inner mitochondrial membrane.
Original research paper: Cell 111, 507 – 518, (2002) |
 | Signalling: Build your own B cell
Rolli and colleagues have devised an alternative reconstruction of B-cell receptor signaling pathways in Drosophila cells. The new system has produced some surprising results, which are reported in Molecular Cell.
Original research paper: Mol. Cell 10, 1057 – 1069, (2002) |
 | Tumour suppressors: Adaptor protein connects to cancer
Alexandra Flemming and colleagues propose that an adaptor protein that is expressed during B-cell development — the SLP65 protein — is a tumor suppressor that limits the proliferation of precursor B cells and promotes their differentiation into mature cells.
Original research paper: Nature Immunol. 4, 38 – 43, (18 Nov 2002) |
 | Neurogenesis: A new target for Hedgehog
New findings indicate that Nmyc is a direct downstream target of Shh that mediates its effects on cell proliferation during cerebellar development and in medulloblastomas.
Original research paper: Development 130, 15 – 28, (2002) |
 | Biotechnology: Putting a finger on gene expression
Writing in Nature Medicine, Rebar, Huang and colleagues describe the first application of a designed zinc finger protein transcription factor in a whole organism.
Original research paper: Nature Med. 8, 1427 – 1432, (2002) |
 | ERK signaling: The next STEP
Paul Lombroso and colleagues show that striatal-enriched tyrosine phosphatase (STEP) may be of importance in regulating the duration of ERK activation and the subsequent downstream signaling cascades that modulate transcription and neuronal function.
Original research paper: Nature Neuroscience 6, 34 – 42, (January 2003) |
 | Ageing: Absence makes the mouse live longer
Knocking out the insulin-like growth factor type 1 receptor (IGF1R) in mice seems to increase their lifespan, suggesting that IGF1R could be a crucial regulator of longevity in mammals.
Original research paper: Nature 11, 287 – 292, (2002 Dec 4) |
 | Natural killer cells: Dual role for NKG2D
Two studies published in Nature indicate that the differential signaling ability of NKG2D, an activating receptor expressed by T cells, depends both on the cell type and the activation state.
Original research paper: Nature Immunol. 3, 1142 – 1149, (2002) |
 | Senescence: Stopping the cycle
Dimitri Lodygin et al. have looked for signaling pathways that specifically downregulate during replicative senescence, and show that treatment of fibroblasts with LY completely and irreversibly inhibits proliferation of the cells by blocking S-phase entry.
Original research paper: J. Clin. Invest. 110, 1717 – 1727, (2002) |
 | Development: Signalling neuronal destiny
Ménard and colleagues report on a new signaling mechanism that allows growth factors to induce progenitor cells to commit to a neuronal lineage.
Original research paper: Neuron 36, 597 – 610, (2002) |
 | Bone diseases: Leptin bares our bones, sympathetically
Karsenty and colleagues have characterized the mechanism by which leptin regulates bone mass, and they show that the sympathetic nervous system is the intermediate between leptin and osteoblasts, and that this mode of action does not affect body weight.
Original research paper: Cell 111, 305 – 317, (2002) |
 | Axon guidance: Mediated Rho by Rho
Yuan et al. examine whether different Rho GTPases have distinct roles in mediating axon guidance when driven by various signals and discover that there is crosstalk between the Cdc42 and RhoA pathways, mediated via the converging actions of these two GTPases on myosin activity.
Original research paper: Nature Cell Biology 5, 38 – 45, (2003) |
 | Transcription: Signal to reshape
Two reports in Science Express reveal that inositol polyphosphates can modulate chromatin-remodeling activity of various complexes including INO80, SNF2 and ISW2.
Original research paper: Nature Rev. Mol. Cell Biol. 3, 422 – 429, (2002) |
 | Apoptosis: Another fragment in the death puzzle
Results from Ding Xue and colleagues indicate that the mitochondrial cell-death pathway is indeed conserved in Caenorhabditis elegans.
Original research paper: Science 298, 1587 – 1592, (2002) |
 | Macrophages: SOCS1 and the innate immune response
Two papers in Immunity now indicate a central role for suppressor of cytokine signaling 1 (SOCS1) in the negative regulation of LPS signaling.
Original research paper: Immunity 17, 583 – 591, (2002) |
 | Obesity: A high dose of JuNK for fat mice
Mice lacking JNK1 suffer less obesity and insulin-resistance than wild-type mice, showing that the elevated expression of JNK1 is a cause of the disease, and not an effect.
Original research paper: Nature 420, 333 – 336, (2002) |
 | Adrenoceptor pharmacology:
Variety is the spice of life
Clark and colleagues present evidence that ß2AR-mediated activation of ERK in HEK293 cells does not require Gi.
Original research paper: Mol. Pharmacol. 62, 1094 – 1102, (2002) |
