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.
 | Neurobiology: Connecting neurexins to synaptic transmission
a-neurexins are required for the activity of presynaptic calcium channels in the synapse, suggesting a new molecular pathway that links synaptic cell adhesion to the machinery for synaptic transmission.
Original research paper: Nature 423, 939 – 948, (2003) |
 | Cell cycle: A supporting role?
Cdk1–cyclin B1 can support replication if it is localized in the nucleus.
Original research paper: Science 300, 987 – 990, (2003) |
 | In brief: June 2003
Signal Transduction | Cell Adhesion | HIV | B-cell Response | Epigenetics | Tumour suppressors |
 | Recombination: Timely interruption
Srs2 prevents untimely recombination intermediates, notably formed during DNA replication, by disrupting the Rad51 nucleofilament.
Original research paper: Nature 423, 305 – 309, (2003) |
 | HIV: Close encounters
HIV can take advantage of intimate contacts between cells of the immune system to aid infection of its principal target, the CD4+ T cell.
Original research paper: Science 300, 1295 – 1297, (2003) |
 | Metastasis: Love thy neighbour
Transcriptional regulation by MTA3 (metastasis-associated gene 3) provides a functional link between loss of expression of ER (estrogen receptor) and loss of expression of E-cadherin.
Original research paper: Cell 113, 207 – 219, (2003) |
 | Angiogenesis: Low pressure warning
Expression of the MET tyrosine kinase — the receptor for hepatocyte growth factor (HGF) encoded by the MET proto-oncogene — is induced by low oxygen tension, activating a programme of invasive growth.
Original research paper: Cancer Cell 3, 347 – 361, (2003) |
 | Stem cells: Harnessing stem cell potential
Sox10 prevents the extinction of two key stem cell properties — proliferation and multipotency — in neural crest stem cells.
Original research paper: Neuron 38, 17 – 31, (2003) |
 | Lead discovery: Piecing together phosphatase inhibitors
A potent non-peptidic protein tyrosine phosphatase 1B inhibitor that shows good selectivity has now been identified.
Original research paper: J. Am. Chem. Soc. 125, 4087 – 4096, (2003) |
 | Mature and mobile: PGE2-EP4 signaling in skin immune responses
Prostaglandin E2-EP4 signaling facilitates the initiation of skin immune responses by promoting the migration and maturation of Langerhans cells.
Original research paper: Nature Medicine 5, 744 – 749, (2003) |
 | Gene regulation: Coordinating opposites
Jane Mellor and colleagues report a new role for forkhead transcription factors 1 and 2 — coordinating early transcription elongation and pre-messenger RNA processing.
Original research paper: Science 300, 492 – 495, (2003) |
 | Signalling: A little fat ... could go a long way
New research has shown that Wnts are palmitoylated and that Wnt signalling can induce self-renewal of haematopoietic stem cells (HSCs).
Original research paper: Nature 423, 409 – 414, (2003) |
 | Lymphopoiesis: Partners in crime
Bcl11a is required for normal B-cell development and functions upstream of Ebf1 and Pax5.
Original research paper: Nature Immunol. 4, 525 – 532, (2003) |
 | Angiogenesis: Interlinked
Pigment epithelium-derived factor (PEDF) secreted by prostate cells is anti-angiogenic and an important contributor to the anticancer effects of androgen ablation.
Original research paper: Nature Med. 9, 774 – 780, (2003) |
 | Anticancer drugs: Switch control
New studies show that SU6668 — a small molecule kinase inhibitor that inhibits signaling through PDGF and VEGF receptors, was most effective in the blocking of late-stage tumors.
Original research paper: J. Clin. Invest. 111, 1287 – 1295, (2003) |
 | Dendrites: Stepping stones to synapse formation
G-protein-coupled receptor kinase-interacting protein 1 (GIT1) acts as an adaptor protein in the pathway to synapse formation and allocation of spine morphology.
Original research paper: J. Cell Biol. 161, 131 – 142, (2003) |
 | Neurodegenerative disease: COX-2 on the brain
New studies show that cyclooxygenase-2 (COX-2) induction after MPTP administration is mediated through a JUN N-terminal kinase/c-JUN-dependent pathway and that neurodegeneration could be reduced by COX-2 inhibitors.
Original research paper: Proc. Natl Acad. Sci. USA 100, 5473 – 5478, (2003) |
 | NMDA receptor trafficking: Enter the exocyst
Synaptic delivery of NMDA receptors from the endoplasmic reticulum to the cell membrane is aided by the formation of a complex containing NMDARs, the exocyst complex and PDZ proteins.
Original research paper: Nature Cell Biology 5, 520 – 530, (2003) |
 | Transcription: Responding to depletion
Richard Treisman's group have now found a missing link in Rho-actin signaling to serum response factor (SRF) — the myocardin-related protein MAL is a globular (G)-actin-responsive SRF coactivator.
Original research paper: Cell 113, 329 – 342, (2003) |
 | Chromatin: Caught in a cage
Terumi Kohwi-Shigematsu and colleagues describe a new model for gene regulation by a nuclear protein — special AT-rich binding protein 1 (SATB1).
Original research paper: Nature Genet. 34, 42 – 51, (2003) |
 | Natural killer cells: A choice of pathways
Studies show that a DAP10-PI3K pathway that is independent of SYK-family protein kinases is a novel mechanism of NK-cell-mediated cytotoxicity.
Original research paper: Nature Immunol. 4, 565 – 572, (2003) |
 | Tumour suppressors: Unexpected relations
Researchers have shown that p53 cooperates with SMAD to control gene expression, thus revealing a new mechanism for the regulation of TGF-ß signaling.
Original research paper: Cell 113, 301 – 314, (2003) |
 | Epigenetics: Less is more
Through the use of a new mouse model, researchers have shown that hypomethylation can cause tumorigenesis through genomic instability.
Original research paper: Science 300, 489 – 492, (2003) |
 | Ion channels: Broken corkscrew
New crystal structure analysis of K+ channels has shown that the previously accepted structural model of K+-gating is fundamentally wrong.
Original research paper: Nature 423, 33 – 41, (2003) |
 | Viral infections: A double whammy for hep C
A HCV enzyme that inhibits IRF-3 activation and two IKK-related kinases that activate IRF-3 and IRF-4 have been found, answering the question of how the hepatitis C virus blocks its host's innate immune response.
Original research paper: Science 300, 1145 – 1148, (2003) |
 | NF?B signaling: IKK-a goes directly for chromatin
IKK-a activates NF-?B-regulated gene expression by phosphorylation of histone H3.
Original research paper: Nature 423, 655 – 659, (2003) |
 | p53 function: Do or die in the fly?
Drosophila melanogaster p53 can normally preserve genome stability by promoting apoptosis alone, but failures in cell-cycle arrest are not required to account for genomic instability.
Original research paper: Proc. Natl Acad. Sci. USA 100, 4696 – 4701, (2003) |
 | Adhesion: Getting to the root of the problem
Researchers now report the identification of desmoglein 4, a desmosomal cadherin which functions in epidermal adhesion and hair-follicle differentiation.
Original research paper: Cell 113, 249 – 260, (2003) |
 | B-cell development: Cast-iron alibi
Zap70, as well as being expressed throughout B-cell development, also has a role in the pro-B- to pre-B-cell transition.
Original research paper: Immunity 18, 523 – 533, (2003) |
 | Therapeutics: Blade runner
The nuclear hormone receptor PPAR-? (peroxisome proliferator-activated receptor-?) functions as a ligand-dependent transcription factor.
Original research paper: J. Clin. Invest. 111, 1381 – 1388, (2003) |
 | Angiogenesis: Skeletal links
The antitumor agent 2-methoxyestradiol (2ME2) — known to have anti-angiogenic properties — dysregulates HIF, a function which is linked to the disruption of the microtubule cytoskeleton.
Original research paper: Cancer Cell 3, 363 – 375, (2003) |
 | Ageing: Looking to the future
A shortage of GABA (?-aminobutyric acid)-mediated inhibition in the visual cortex might underlie age-related visual deficits.
Original research paper: Science 300, 812 – 815, (2003) |
 | Obesity: Turning on fat burning
The ligand-activated transcription factor PPAR-d stimulates fat burning, which indicates that drugs that activate PPAR-d might have potential for treating obesity.
Original research paper: Cell 113, 159 – 170, (2003) |
