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.
 | Quantitative proteomics: A new approach to an old pathway
A new proteomic approach provides a temporal view of epidermal growth factor-induced phosphotyrosine signaling.
Original research paper: Nature Biotechnology 22, 1139 – 1145, (2004) |
 | Cytoskeleton: A joint effort
The GEF activity of Dock180 and the pleckstrin homology (PH) domain of ELMO function in trans to regulate Rac activation.
Original research paper: Nature Struct. Mol. Biol. 11, 756 – 762, (2004) |
 | In brief: September 2004
Cell adhesion | Cell proliferation | T-cell memory | Lymphoid architecture | Inflammation | Targeted therapy | Tumour suppressors | Neurotransmission | Regeneration | Anticancer drugs | Imaging | Biotechnology |
 | Developmental biology: Putting up barriers
The limb bud Sonic hedgehog–fibroblast growth factor (Shh–Fgf) feedback loop is terminated by the expansion of former SPA cells.
Original research paper: Science 305, 396 – 399, (2004) |
 | Lymphocyte responses: Linking arms
Interleukin-5 (IL-5) provides a novel pathway linking the adaptive and natural arms of the immune system.
Original research paper: J. Clin. Invest. 114, 427 – 437, (2004) |
 | T-cell development: Location, location, location
Signaling through the CC-chemokine receptor 7 (CCR7) is crucial for intrathymic migration and for the maintenance of thymic architecture.
Original research paper: J. Exp. Med. 200, 481 – 491, (2004) |
 | Cachexia: A bit of muscle
Cachetic factors — such as the cytokines tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ) — selectively target the myosin heavy chain (MYHC).
Original research paper: J. Clin. Invest. 114, 370 – 378, (2004) |
 | Hypoxia: Structural disruption
A small molecule has been discovered that disrupts the structure of a key coactivator in the hypoxia-inducible factor (HIF) pathway and inhibits tumor growth in vivo.
Original research paper: Cancer Cell 6, 33 – 43, (2004) |
 | Epigenetics: Family feud
The imprinted signaling protein XLas is required for postnatal adaptation to feeding.
Original research paper: Nature Genet. 36, 818 – 826, (2004) |
 | Synaptogenesis: New players in presynaptic organization
Members of the fibroblast growth factor (FGF) family have an important role in presynaptic organization.
Original research paper: Cell 118, 257 – 270, (2004) |
 | Beyond botox: Deadly venoms as potent research tools
Evolution has provided certain snakes and snails with a variety of toxins; by tethering these compounds to cell membranes, one lab has found the means to move beyond knockouts with a more refined strategy for the targeted inactivation of specific receptors and signaling proteins.
Original research paper: Neuron 43, 305 – 311, (2004) |
 | PI3K signaling: Calcium channels on the move
PI3Kγ signaling through Akt/PKB induces voltage-gated calcium channel trafficking to the plasma membrane in excitable cells.
Original research paper: Nature Neuroscience 7, 939 – 946, (2004) |
 | Cell migration: A move away from death
Better known for its anti-apoptotic abilities, Drosophila inhibitor of apoptosis (DIAP) also functions independently of this role, in Rac-mediated cell motility.
Original research paper: Cell 118, 111 – 125, (2004) |
 | Developmental biology: Separating head from tail
Graded activin signaling can establish A–P polarity and trigger convergent extension, whereas Nodal is likely to be responsible for the control of A–P patterning in vivo.
Original research paper: Nature 430, 364 – 367, (2004) |
 | Immune regulation: Driving DC differentiation
Activation of peroxisome proliferative activated receptor-γ (PPARγ) specifies a dendritic cell subtype that is capable of an enhanced induction of iNKT cell expansion.
Original research paper: Immunity 21, 95 – 106, (2004) |
 | Immunogenetics: KIRs resolve the issue
An inhibitory NK-cell receptor — KIR2DL3 — and its ligand affect the outcome of infection with hepatitis C virus (HCV).
Original research paper: Science 305, 872 – 874, (2004) |
 | Tumorigenesis: Specific non-cooperation
A complex and sometimes mutually exclusive relationship exists between the Pten and Ras pathways in skin tumor progression.
Original research paper: Genes Dev. 18, 1800 – 1805, (2004) |
 | Breast cancer: Getting to know the neighbours
All cell types in mammary tissue undergo changes in gene expression during cancer progression, indicating that each of these components contributes to the development of breast cancer.
Original research paper: Cancer Cell 6, 17 – 32, (2004) |
 | Technology: No-bake recipe for DNA
Using a bacterial helicase instead of heat to denature the template overcomes the limitations of PCR by devising a means to amplify DNA at a single temperature.
Original research paper: EMBO Reports 5, 795 – 800, (2004) |
 | Axon guidance: Translating the cues
Semaphorin3A (SEMA3A) induces axonal transport by activating a translation-initiation factor at the growth cone — a process that depends on the tyrosine kinase FYN and the cyclin-dependent kinase 5 (CDK5).
Original research paper: J. Neurosci. 24, 6161 – 6170, (2004) |
 | Neurodegenerative disorders: SOD1 targeting in ALS
Mutant Cu/Zn superoxide dismutase (SOD1) interacts with the mitochondria by binding with B-cell leukaemia/lymphoma-2 (BCL2), which in turn leads to accelerated cell death.
Original research paper: Neuron 43, 5 – 17, (2004) |
 | TGF-beta signaling: cPML holds the key
Cytoplasmic promyelocytic leukemia (cPML) tumor suppressor protein isoforms are implicated in TGF-ß signaling, which is impaired in acute promyelocytic leukemia (APL).
Original research paper: Nature 431, 205 – 211, (09 September 2004) |
 | Protein degradation: Be more choosy
Multiubiquitin chain receptors can add a further layer of substrate selectivity in the ubiquitin-proteasome system.
Original research paper: Cell 118, 99 – 110, (2004) |
 | Nuclear transport: New role for an old favourite
The yeast centrin Cdc31 has an unexpected role in the nuclear mRNA export machinery.
Original research paper: Nature Cell Biol. 6, 840 – 848, (2004) |
 | Mucosal immunology: Recognizing the good guys
Toll-like receptor-mediated recognition of commensal bacteria is important for maintaining epithelial integrity and for tissue repair.
Original research paper: Cell 118, 229 – 241, (2004) |
 | Therapeutics: Pinch hitter
A newly identified compound — which inhibits the kinase activity of BCR-ABL — may offer a powerful treatment for chronic myeloid leukaemia.
Original research paper: Science 305, 399 – 401, (2004) |
 | Neurogenesis: VEGF — a route to new neurons
The induction of hippocampal neurogenesis is mediated through one of the receptors for VEGF, the kinase insert domain protein receptor (KDR).
Original research paper: Nature Genet. 36, 827 – 835, (2004) |
 | Metabolic syndrome: Outside the site: a lateral approach to phosphatase inhibition
Allosteric inhibition of the protein tyrosine phosphatase-1B (PTP1B) prevents formation of the active conformation of the enzyme by blocking mobility of the catalytic loop.
Original research paper: Nature Struct. Mol. Biol. 11, 730 – 737, (2004) |
 | Imaging and Visualization: What Lies Beneath-Tracking Tumors with Quantum Dots
Quantum dots (QDs) are rapidly becoming the reagent of choice for a variety of imaging applications; now, for the first time, a team of investigators demonstrates their applicability for the targeted, noninvasive imaging of tumors in live animals.
Original research paper: Nat Biotechnol 22, 969 – 976, (2004) |
 | Translation: Building with new blocks
In certain organisms the usual complement of 20 amino acids is enhanced by two further ones encoded by stop codons. One of these, pyrrrolysine, is directly attached to the tRNA, providing the first example of the charging of a tRNA with a non-canonical amino acid.
Original research paper: Nature 431, 333 – 335, (16 September 2004) |
 | RNA interference: A slice of the action
Two collaborative papers now provide convincing evidence that Argonaute is the enzyme that mediates mRNA cleavage during RNA interference (RNAi).
Original research paper: Science 305, 1437 – 1441, (2004) |
 | Viral immunity: Retroviral TRIMming
The TRIM family of cytoskeletal proteins might have a widespread, evolutionarily conserved role in innate immunity to retroviral infection.
Original research paper: Proc. Natl Acad. Sci. USA 101, 10774 – 10779, (2004) |
 | Signal transduction: Time for a 'signal-o-some'?
A new way to measure activation of phosphoprotein-driven signaling has been developed, which correlates the activity of different networks with the response of AML cells to therapy.
Original research paper: Cell 118, 217 – 228, (2004) |
 | Evo–Devo: Vertebrate face in profile
Studies of zebrafish that are mutant for integrin-a5 have revealed a new link between integrins and face patterning.
Original research paper: PLoS Biol. 2, E244(2004) |
 | Ion channels: Temperature sensitivity is voltage dependent
We are now a step closer to understanding the mechanism by which gating occurs in temperature-sensitive TRP channels.
Original research paper: Nature 430, 748 – 754, (2004) |
 | Drug metabolism: Small but significant
The crystal structure of arguably the most important enzyme in drug metabolism – cytochrome P450 3A4 (CYP3A4) – has been published, and with it comes the surprise discovery that its active site is much smaller than previously thought.
Original research paper: Science 305, 683 – 686, (2004) |
