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.
 | Hedgehog signaling: A Smoothened operator
Protein kinase A and casein kinase I directly regulate Smoothened activity to promote Hedgehog signal transduction.
Original research paper: Nature 432, 1045 – 1050, (23 December 2004) |
 | Mechanism of disease: The stresses of weight gain
Obesity-induced endoplasmic reticulum stress in peripheral tissues may be a key mechanism in triggering insulin resistance and type-2 diabetes.
Original research paper: Science 306, 457 – 461, (2004) |
 | In brief: December 2004
Microrna | Cytoskeleton | Innate Immunity | Regulatory T Cells | Apoptosis | Inflammation | Cytokines | Protein Kinases | Immunology | Angiogenesis | Gene expression | Functional genomics | Development | Cell Biology of the Neuron | Lung diseases |
 | Innate Immunity: The fight for iron
In response to Toll-like receptor (TLR) triggering the innate immune system produces lipocalin-2, thus preventing bacteria from obtaining the iron that is essential to their growth and survival.
Original research paper: Nature 432, 917 – 921, (2004) |
 | Receptor tyrosine kinases: Getting on TRK
An alternative splicing mechanism has been identified that causes neuroblastoma cells to switch from expressing a growth-inhibiting form of the receptor tyrosine kinase TRKA to producing an oncogenic form that promotes tumor progression.
Original research paper: Cancer Cell 6, 347 – 360, (2004) |
 | Technology: Express delivery
Retroviral vectors can now be used to deliver DNA and protein in an efficient, dose-controlled, transient and targeted manner.
Original research paper: Mol. Cell 16, 309 – 315, (2004) |
 | Addiction: Identity of reward
Activation of α4 nicotinic acetylcholine receptors (nAChRs) is sufficient to mediate nicotine-induced reward, tolerance and sensitization.
Original research paper: Science 306, 1029 – 1032, (2004) |
 | Kinases: Making gains on glioma
A small-molecule inhibitor of transforming growth factor-β (TGF-β) receptor I kinase could prove to be an effective treatment for human gliomas.
Original research paper: Cancer Res. 64, 7954 – 7961, (2004) |
 | Genomics: High-throughput matchmaking
By modifying the yeast one-hybrid assay, a new screen has been developed that has a high-throughput potential for matching transcription factors and promoters in Caenorhabditis elegans.
Original research paper: Genome Res. 14, 2093 – 2101, (2004) |
 | Bacterial pathogenesis: Cheating death
The intracellular pathogen Chlamydia can inhibit the programmed cell death of the cells it infects by eliminating pro-apoptotic proteins.
Original research paper: J. Exp. Med. 200, 905 – 916, (2004) |
 | Signaling crosstalk: All roads lead to Groucho
EGF receptor signaling attenuates Groucho-dependent transcriptional repression and antagonizes the Notch signaling pathway.
Original research paper: Nature Genetics 37, 101 – 105, (12 December 2004) |
 | Technique:
Cellular cartography
A new imaging technique allows the analysis of complex biological phenomena such as integrin dynamics during cell migration.
Original research paper: J. Cell Sci. 117, 5521 – 5534, (2004) |
 | MicroRNA:
Big secrets of a small world
Micro RNA (miRNA) genes are transcribed by RNA polymerase II (pol II).
Original research paper: EMBO J. 23, 4051 – 4060, (2004) |
 | Macrophages:
Common clearance pathway
A common transcriptional pathway is used by macrophages to facilitate the clearance of both oxidatively modified lipoproteins and phagocytosed intracellular bacteria.
Original research paper: Cell 119, 299 – 309, (2004) |
 | Metastasis: Causing cancer spread
Platelet-derived growth factor (PDGF)-BB and its receptor tyrosine kinase PDGFR promote lymphangiogenesis and lymphatic metastasis.
Original research paper: Cancer Cell 6, 333 – 345, (2004) |
 | Protein kinases: REDD or dead?
REDD1 is required for the hypoxia-induced inactivation of the protein kinase mammalian target of rapamycin (mTOR).
Original research paper: Genes Dev. 18, 2893 – 2904, (2004) |
 | Developmental genetics: Controlling elements come of age
Retrotransposons have an important role in gene regulation — possibly by controlling chromatin states.
Original research paper: Dev. Cell 7, 597 – 606, (2004) |
 | Development: Having the NRG to migrate
Neuregulin-1 is a chemoattractant in the tangential migration of inhibitory interneurons from the medial ganglionic eminences to the cortex.
Original research paper: Neuron 44, 251 – 261, (2004) |
 | Neurodegenerative disease: Body-building for small molecules
A novel strategy has been developed that overcomes the difficulties associated with designing small molecule drugs to combat Alzheimer's disease.
Original research paper: Science 306, 865 – 869, (2004) |
 | Drug discovery: Getting past the pump
An assay integrating chemical screening and suppressor gene determination promises to accelerate the identification of potent antibacterial compounds and their target proteins.
Original research paper: Chem. Biol. 11, 1423 – 1430, (2004) |
 | Bacterial pathogenesis: Exterior detection
The extracellular pathogen Helicobacter pylori stimulates a pro-inflammatory response through its type IV secretion system (T4SS), this delivers a peptidoglycan motif that is recognized by the host intracytoplasmic sensor Nod1.
Original research paper: Nature Immunol. 5, 1166 – 1174, (2004) |
 | Morphogenetic movements: Less Wnt from Kaiso
Non-canonical Wnt signals are modulated by Kaiso and p120-catenin as part of a new developmental pathway that regulates vertebrate morphogenesis.
Original research paper: Nature Cell Biology 6, 1212 – 1220, (2004) |
 | Epigenetics: Let us join together in silence
RITS (RNA-induced initiation of transcriptional gene silencing) binding to heterochromatic loci enables RNAi machinery to function in cis to destroy aberrant RNAs and generate siRNAs for heterochromatin maintenance.
Original research paper: Nature Genet. 36, 1174 – 1180, (2004) |
 | Cell spreading: Come closer to the edge
Rap1 mediates Rac-dependent cell spreading by localizing Rac guanine nucleotide exchange factors (GEFs) to the appropriate cellular sites.
Original research paper: J. Cell Biol. 167, 111 – 122, (2004) |
 | Macrophages: New anti-inflammatory pathway
Nicotine and acetylcholine signaling inhibits the accumulation of the endotoxin-induced high-mobility group box 1 (HMGB1) in macrophages and thus delays the onset of sepsis.
Original research paper: Nature Med. 10, 1216 – 1221, (2004) |
 | Metastasis: No way out?
Semaphorin 3F (SEMA3F) — an axon guidance regulator — can inhibit melanoma metastatic spread and angiogenesis.
Original research paper: J. Clin. Invest. 114, 1260 – 1271, (2004) |
 | Tumour suppressors: Super suppressor
Super transgenic mice that express an additional copy of Ink4a/Arf, serve as a model to study the consequences of increased expression of tumor suppressor genes.
Original research paper: Genes Dev. 18, 2736 – 2746, (2004) |
 | RNA interference: Silencing the sceptics
The first demonstration of the in vivo silencing by small interfering RNA (siRNA) of an endogenous gene — apolipoprotein B (APOB) — gives great promise for using RNA interference as a potential approach to treating disease.
Original research paper: Nature 432, 173 – 178, (2004) |
 | Behavioural neuroscience: Of food and danger
Studies in Caenorhabditis elegans show that serotonin can signal the presence of food and lead to rapid and reversible changes in the worm's avoidance of the noxious odor octanol.
Original research paper: Proc. Natl Acad. Sci. USA 101, 15512 – 15517, (2004) |
 | Biosensors: Hybridization chain reaction
A new technique, based on a chain reaction of recognition and hybridization events between two sets of DNA hairpin molecules, offers an enzyme-free alternative for the rapid detection of specific DNA sequences.
Original research paper: Proc. Natl. Acad. Sci. USA 101, 15275 – 15278, (2004) |
 | Bacterial physiology: E. coli shape up
Ftsz, in addition to regulating bacterial cell division, also has a role in determining cell morphology.
Original research paper: J. Bacteriol. 186, 6768 – 6774, (2004) |
 | Oncogenic and oxidative stress: Seladin-1 at the crossroads
Seladin-1 regulates the p53-mediated cellular response to oxidative stress and Ras-induced cellular senescence.
Original research paper: nature 432, 640 – 645, (02 December 2004) |
 | Adhesion and signalling: The many faces of β-catenin
β-catenin acquires distinct molecular forms with different binding properties that regulate its roles in adhesion and Wnt signaling.
Original research paper: J. Cell Biol. 167, 339 – 349, (2004) |
 | Transcription: What dREAMs are made of
Two new receptor complexes – recruited by retinoblastoma protein (pRb) to E2F-bound gene promoters – have been isolated from the fruit fly and named dREAM (Drosophila RBF, E2F and Myb-interacting proteins).
Original research paper: Cell 119, 181 – 193, (2004) |
 | T-cell responses: NK cells set a prime example
After stimulation with mature DCs or certain adjuvants, natural killer (NK) cells are recruited to the lymph nodes where they participate in T-cell polarization by producing interferon-γ (IFN-γ).
Original research paper: Nature Immunol. 5, 1260 – 1265, (2004) |
 | Mast cells: Adaptors have pluses and minuses for mast cells
The mast cell transmembrane adaptor protein NLAT (non-T-cell activation linker) functions as both a negative and positive regulator of FcεRI-mediated signaling.
Original research paper: J. Exp. Med. 200, 991 – 1000, (2004) |
 | Kinase inhibition: Life and LYN
The ability of BCR–ABL1 to interact with the tyrosine kinase LYN and promote cell survival may be a key event in BCR–ABL1's cell transformation potential.
Original research paper: Nature Med. 10, 1187 – 1189, (2004) |
 | Drug resistance: Multiple opponents
The tyrosine kinase inhibitor drug imatinib (Glivec) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump.
Original research paper: Blood 104, 2940 – 2942, (2004) |
 | Technology: Targeting the worm
A new method based on transposon-mediated gene conversion has finally made targeted gene disruption in Caenorhabditis elegans possible.
Original research paper: Nature Genetics 36, 1231 – 1237, (2004) |
 | Synaptic function: Adapting to epilepsy
AP-3B, the neuron-specific member of the adaptor complex (AP) protein family, has a role in the regulation of GABA (γ-aminobutyric acid) release and may also be involved in the pathogenesis of epilepsy.
Original research paper: J. Cell Biol. 167, 293 – 302, (2004) |
 | Synaptic plasticity: Steps to lasting plasticity
Tissue plasminogen activator (tPA) and brain derived neurotrophic factor (BDNF) are intimately linked in the control of long-term potentiation (L–LTP).
Original research paper: Science 306, 487 – 491, (2004) |
 | Memories are made of this
A photoreactive antagonist has been developed that allows precise temporal and spatial inactivation of a neuronal ion–channel receptor, and promises to elucidate the receptor's role in memory formation.
Original research paper: J. Am. Chem. Soc. 126, 13886 – 13887, (2004) |
 | Protozoan parasites: Reversible entry
New light has been shed on the molecular mechanisms used by Trypanosoma cruzi to enter host cells and establish a productive infection.
Original research paper: J. Exp. Med. 200, 1135 – 1143, (2004) |
