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.
 | Obesity: AMP-kinase thinks thin
Hypothalamic AMPK mediates hormonal and nutrient-derived feeding signals that can lead to obesity.
Original research paper: Nature 428, 569 – 574, (17 March 2004) |
 | Ageing: Long live SIRT1
A link exists between the NAD-dependent protein deacetylase SIRT1, forkhead transcription factor FOXO3a and mammalian longevity.
Original research paper: Cell 116, 551 – 563, (2004) |
 | In brief: March 2004
Apoptosis | Signal Transduction | Cell Adhesion | T-cell Signalling | Dendritic Cells | T-Cell Activation | Tolerance | Tumour Immunity | T-cell Responses | Metastasis | Sensory physiology | Neural modulation | Anticancer drugs | Kinases |
 | Antigen presentation: Shocking stimulation
HSP70 peptide binding mutants separate antigen delivery from dendritic cell stimulation.
Original research paper: Immunity 20, 95 – 106, (2004) |
 | T-cell signalling: Giving T cells a PEP talk
PEST—domain—enriched tyrosine phosphatase (PEP) has a specific role in dampening the response of effector/memory T cells to T-cell receptor stimulation.
Original research paper: Science 303, 685 – 689, (2004) |
 | Viral immunity: Silencing the silencers
Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing.
Original research paper: Proc. Natl Acad. Sci. USA 101, 1350 – 1355, (2004) |
 | Angiogenesis: Going for the double
Integrin-linked kinase (ILK) has two key roles in tumor angiogenesis, and is therefore a promising new target for anti-angiogenic therapies.
Original research paper: Cancer Cell 5, 79 – 90, (2004) |
 | Tumour suppressors: Conflict resolution
Activation of nuclear hormone receptor Pparß/d accelerates intestinal adenoma growth.
Original research paper: Nature Med. 10, 245 – 247, (2004) |
 | Sensory systems: The flavour of long life
Gustatory neurons seem to act through the DAF–2 pathway to regulate longevity.
Original research paper: Neuron 41, 45 – 55, (2004) |
 | Pain: The pain of integrins
Integrin signaling may have a role in inflammatory and neuropathic pain in the rat.
Original research paper: Eur. J. Neurosci. 19, 634 – 642, (2004) |
 | T cell anergy: An NFATic response
The prevention of autoimmunity by T cell anergy is controlled by a complex multistep negative signaling pathway, requiring the coordinated action of several E3 ubiquitin ligases.
Original research paper: Nature Immunology 5, 255 – 265, (March 2004) |
 | Cell cycle: Sisters stick together
The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis.
Original research paper: Nature 427, 510 – 517, (2004) |
 | Cell growth: Testing the water
Regulation of polarized growth initiation and termination cycles by the polarisome and Cdc42 regulators.
Original research paper: J. Cell Biol. 164, 207 – 218, (2004) |
 | Immune responses: Helping T cells to relax and interact
Inactivation of Ezrin—Radixin—Moesin proteins through a Vav1—Rac1 pathway leads to relaxation of the T—cell cytoskeleton and favours conjugate formation with antigen presenting cells.
Original research paper: Nature Immunol. 3, 110 – 122, (8 February 2004) |
 | Tumorigenesis: Nuisance neighbours
Loss of transforming growth factor-ß (TGF-ß) signaling in stromal fibroblasts leads to oncogenic changes in adjacent epithelial cells.
Original research paper: Science 303, 848 – 851, (2004) |
 | Cardiovascular disease: Healing hearts
Infarct size and reperfusion injury is reduced by cytochrome P450 monooxygenase (CYP) inhibitors.
Original research paper: Proc. Natl Acad. Sci. USA 101, 1321 – 1326, (2004) |
 | Calcium signaling: The heart of PKC function
Stimulation of PKC-a in cardiac myocytes reduces phospholamban (PLB) phosphorylation, resulting in diminished myocyte contractile force and influencing susceptibility to heart failure.
Original research paper: Nature Medicine 10, 248 – 254, (2004) |
 | Cellular microbiology: Two types of tail
The RickA protein of Rickettsia conorii activates the Arp2/3 complex.
Original research paper: Nature 427, 457 – 461, (2004) |
 | Protein Degradation: Take a leaf from plants
Human DET1 promotes the ubiquitylation and degradation of c-Jun by promoting ubiquitin-ligase-complex assembly.
Original research paper: Science 303, 1371 – 1374, (2004) |
 | T-cell development: Survivin against the odds
Survivin, a member of the inhibitor of apoptosis protein family, has an important role in T-cell development.
Original research paper: J. Exp. Med. 199, 69 – 80, (2004) |
 | Therapeutics: Overcoming inhibition
Small molecule inhibitors remove an important 'brake' in apoptosis, stripping tumors of their immortality.
Original research paper: Cancer Cell 5, 25 – 35, (2004) |
 | Cancer genetics:
p53, a protein with a pulse
Research has now shed light on the dynamics of the p53—Mdm2 feedback loop in individual cells.
Original research paper: Nature Genet. 36, 147 – 150, (2004) |
 | Synaptic physiology: Putting receptors in their place
PD95 controls the incorporation of AMPA receptors into the postsynaptic membrane during plasticity both in vitro and in vivo.
Original research paper: J. Neurosci. 24, 916 – 927, (2004) |
 | Cell cycle: Stress management
The MKK7-JNK-c-Jun signaling pathway regulates CDC2 expression, directly linking stress and developmental signals to G2/M cell cycle progression.
Original research paper: Nature Cell Biology 6, 215 – 226, (2004) |
 | RNA splicing:
Some don't like it hot
Dephosphorylated SRp38 acts as a splicing repressor in response to heat shock.
Original research paper: Nature 427, 553 – 558, (2004) |
 | Haematopoiesis:
Death-defying factor identified
Anamorsin is a novel anti-apoptotic factor that is induced by cytokines during definitive hematopoiesis.
Original research paper: J. Exp. Med. 199, 581 – 592, (2004) |
 | Metastasis:
Migratory cues
ERBB2 and transforming growth factor-ß (TGF-ß) work together to cause invasion and migration of breast cancer cells.
Original research paper: Proc. Natl Acad. Sci. USA 101, 1257 – 1262, (2004) |
 | Tumour suppressors:
A topsy-turvy world
Ovca1 regulates cell proliferation, embryonic development and tumorigenesis.
Original research paper: Genes Dev. 18, 320 – 332, (2004) |
 | Neurological Disorders:
A convergence point in MS pathology
Cytosolic phospholipase A2 plays a key role in the pathogenesis of multiple sclerosis-like disease.
Original research paper: Neuron 41, 323 – 335, (2004) |
 | GPCRs:
Family traits
One approach to ligand discovery for GPCRs in class A could involve analysis of the receptor binding pocket to see whether a particular privileged-structure-binding region is present.
Original research paper: J. Med. Chem. 47, 888 – 899, (2004) |
