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.
 | Proteomics: Getting from TNF-α to NF-κB
The TNF-α/NFκB signaling pathway has been mapped using a large-scale functional proteomics approach to show hundreds of molecular associations and 80 novel interactors.
Original research paper: Nature Cell Biology 6, 87 – 89, (2004) |
 | Membrane dynamics: Cholesterol goes global
PtdIns(4,5)P2 depletion regulates the actin cytoskeleton in a similar manner to cholesterol depletion.
Original research paper: Proc. Natl Acad. Sci. USA 100, 13964 – 13969, (2003) |
 | In brief: January 2004
Nuclear export | Phagocytosis | Cytoskeleton | Autoimmunity | Gene regulation | Hiv | T-cell development | Transplantation | Therapeutics | Tumour progression | Clinical trials | Tumour suppressors | Cell biology of the neuron | Anticancer Drugs |
 | Viral Immunity: Role for Bim in termination of immune responses
The BH3-only pro-apoptotic BCL-2-family member Bim is a crucial inducer of programmed cell death in the lymphoid lineage.
Original research paper: Proc. Natl Acad. Sci. USA 100, 14175 – 14180, (2003) |
 | T-cell responses: The choice between anergy or activity
Two isoforms of otubain 1 regulate T cell anergy via GRAIL.
Original research paper: Nature Immunol. 5, 45 – 54, (2004) |
 | Tumorigenesis: Flying beneath the radar
Constitutive activation of the Stat3 transcription factor in tumors inhibits dendritic cell maturation and prevents the immune system from eliminating the tumor.
Original research paper: Nature Med. 10, 48 – 54, (2004) |
 | Developmental genetics: The making of a male
Testis determination requires insulin receptor family function in mice.
Original research paper: Nature 426, 291 – 295, (2003) |
 | Neurological disorders: Fragile X functions
The fragile X mental retardation protein is required for type-1 metabotropic glutamate receptor-dependent translation of PSD-95.
Original research paper: Proc. Natl Acad. Sci. USA 100, 14374 – 14378, (2003) |
 | Neurological disorders: Protecting against hypoglycaemia
Cortical cultures derived from PARP1-knockout mice, or cultures treated with a PARP1 inhibitor, are largely resistant to hypoglycaemic neuronal death.
Original research paper: J. Neurosci. 23, 10681 – 10690, (2003) |
 | Structure-based drug design: Anthrax attacked!
Two papers report the identification of small molecule inhibitors of anthrax toxin.
Original research paper: Nature Struct. Mol. Biol. 11, 60 – 66, (2004) |
 | Pluripotency: Not Wnting to differentiate
The Wnt signaling pathway is the first signaling system known to be required to maintain the undifferentiated state of both mice and human pluripotent embryonic stem cells.
Original research paper: Nature Medicine 10, 55 – 63, (2004) |
 | Membrane traffic: Stimulating curves
Lipid packing sensed by ArfGAP1 couples COPI coat disassembly to membrane bilayer curvature.
Original research paper: Nature 426, 563 – 566, (2003) |
 | Immune regulation: Overactive cytokines
Two studies have revealed a new role for WSX1 as a negative regulator of the cytokine response to intracellular pathogens.
Original research paper: Immunity 19, 657 – 667, (2003) |
 | T-cell memory: Staying alive with IL-7
Interleukin-7 has an imporant role in the generation and maintenance of CD4+ memory T cells.
Original research paper: J. Exp. Med. 198, 1807 – 1815, (2003) |
 | Therapeutics: Heading for a cure
A small-molecule antagonist of Cxcr4 inhibits intracranial growth of primary brain tumors.
Original research paper: Proc. Natl Acad. Sci. USA 100, 13513 – 13518, (2003) |
 | Glia: A time code for myelin
A combinatorial network of evolutionarily conserved myelin basic protein regulatory sequences confers distinct glial-specific phenotypes.
Original research paper: J. Neurosci. 23, 10214 – 10223, (2003) |
 | Neurodegenerative disease: Shifting the cut of APP
Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Aß42by inhibiting Rho.
Original research paper: Science 302, 1215 – 1217, (2003) |
 | Ras signaling: Putting IMP on the signaling MAP
Ras regulates MAP kinase signaling by derepressing Impedes Mitogenic signal Propagation (IMP)- induced Raf-MEK complex formation. IMP modulates the sensitivity of the MAP kinase cascade to stimulus-dependent activation.
Original research paper: Nature 427, 256 – 260, (15 January 2004) |
 | Chromatin: Keep it level
Research has unveiled a Rad53 kinase-dependent surveillance mechanism that regulates histone protein levels in yeast.
Original research paper: Cell 115, 537 – 549, (2003) |
 | Exocytosis: Rapid-response unit
PIP2 increases the speed of response of synaptotagmin and steers its membrane-penetration activity toward the plasma membrane.
Original research paper: Nature Struct. Mol. Biol. 3, 36 – 44, (2004) |
 | Innate immunity: Differential TLR signalling
Signaling through TLRs can result in qualitative differences in immune responses by a mechanism involving differential ERK signaling and c-FOS.
Original research paper: J. Immunol. 171, 4984 – 4989, (2003) |
 | Breast cancer: EMSY forges a link
EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer.
Original research paper: Cell 115, 523 – 535, (2003) |
 | Prostate cancer: Acting alone
Molecules that are designed to specifically target the ligand-binding domain of androgen-receptors may effectively treat hormone-refractory prostate cancer.
Original research paper: Nature Med. 10, 33 – 39, (2004) |
 | Development: Charting neural induction
Two reports dissect out the downstream signals that mediate the dual responses to FGF in two different species.
Original research paper: Cell 115, 603 – 613, (2003) |
 | Development: Signaling left and right
The Notch signaling pathway regulates left-right determination by detecting a transient build-up of extracellular calcium around the left side of the node, which is caused by an asymmetrical reduction in H+/K+-ATPase activity.
Original research paper: Nature 427, 121 – 128, (08 January 2004) |
 | Endocytosis: A propelling pathway
A recent paper outlines a role for actin in the internalization of the budding yeast endocytic complex.
Original research paper: Cell 115, 475 – 487, (2003) |
 | Autoimmunity: T cells escape deletion
A Nature paper describes a mouse model of autoimmune arthritis in which disease is caused by a single point mutation, altering the threshold of T-cell receptor signaling and enabling autoreactive T cells to avoid deletion.
Original research paper: Nature 426, 454 – 460, (2003) |
 | Lymphocyte development: Shared survival signals
Researchers have now identified the BCL-2-family member myeloid-cell leukaemia 1 as a crucial component of the signaling pathway downstream of IL-7.
Original research paper: Nature 426, 671 – 676, (2003) |
 | Extracellular matrix: Sparcs turn into flames
Stromal cells produce a secreted protein, acidic and rich in cysteine—Sparc—that helps organize the basement-membrane structure that is required for tumor progression.
Original research paper: J. Exp. Med. 198, 1475 – 1485, (2003) |
 | Cell biology of the neuron: Endocytic partnership
Two complementary articles shed light on the function of endophilin and synaptojanin in vivo and highlight the importance of a direct interaction between them for endocytosis to occur.
Original research paper: Neuron 40, 733 – 748, (2003) |
 | Target validation: Of mice and men and rats...
There are marked differences between the distribution and pharmacology of a particular serotonin receptor subtype in humans and rats, and that observed in mice.
Original research paper: Mol. Pharmacol. 64, 1295 – 1308, (2003) |
