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.
 | Wnt signaling: Poles apart
During zebrafish gastrulation the cells present in the dorsal epiblast preferentially divide along the animal-vegetal axis of the embryo under the control of non-canonical Wnt signaling.
Original research paper: Nature 430, 689 – 693, (05 August 2004) |
 | Cytoskeleton: A signal to collapse
An interaction with the collagen receptor a2ß1 followed by unique intracellular signaling causes actin stress fibres and focal adhesions to break down and stops endothelial-cell migration in its tracks, thereby preventing capillary formation.
Original research paper: J. Cell Biol. 166, 97 – 109, (2004) |
 | In brief: July 2004
Cell cycle | Gene transcription | Morphogenesis | Innate Immunity | Asthma and Allergy | Signalling | Innate Immunity | Lymphocyte Signalling | Ageing | Development | Lead identification | Imaging |
 | Cytokinesis: A good place to start
An approach that combines functional-proteomic and comparative-genomic analysis has been used in the identification and characterization of proteins that function in cytokinesis.
Original research paper: Science 305, 61 – 66, (2004) |
 | Stem Cells: Getting a replacement
Male germline stem cells in the Drosophila melanogaster testis can be replaced by dedifferentiated spermatogonia, which then repopulate the stem-cell microenvironment.
Original research paper: Science 304, 1331 – 1334, (2004) |
 | Angiogenesis: Recruitment drive
VEGF-null cells require PDGFRα signaling-mediated stromal fibroblast recruitment for tumorigenesis.
Original research paper: EMBO J. 23, 2800 – 2810, (2004) |
 | Synaptic plasticity: The highs and lows of synaptic plasticity
The subunit composition of NMDA receptors might be the determining factor in the direction of hippocampal plasticity.
Original research paper: Science 304, 1021 – 1024, (2004) |
 | Dermatitis: Getting skin deep with IL-31
A newly identified and characterized cytokine, IL-31, may be involved in promoting the dermatitis and epithelial responses that characterize allergic and non-allergic diseases.
Original research paper: Nature Immunology 5, 752 – 760, (July 2004) |
 | Cell polarity: Polar exploration
An actin-like gene can determine cell polarity in bacteria.
Original research paper: Proc. Natl Acad. Sci. USA 101, 8643 – 8648, (2004) |
 | Innate immunity: Cargo-driven phagosome fate
Activation of Toll-like receptor signaling by bacteria, but not by apoptotic cells, underlies the distinct outcomes of phagocytic pathways.
Original research paper: Science 304, 1014 – 1018, (2004) |
 | Antigen presentation: Presenting a newly charged antigen
Certain polysaccharides, when processed by antigen-presenting cells, can associate with MHC class II molecules and induce CD4+ T-cell responses.
Original research paper: Cell 117, 677 – 687, (2004) |
 | Tumour suppressors: The PUMA effect
The p53-regulated protein PUMA is required to suppress tumorigenesis in some contexts, such as expression of Myc or a combination of E1A and RAS, but not in others, such as expression of RAS alone.
Original research paper: Proc. Natl Acad. Sci. USA 101, 9333 – 9338, (2004) |
 | Glia: A new release from astrocytes
Astrocytes release glutamate through a SNARE-dependent exocytic mechanism, which is strikingly similar to the mechanism of neurotransmitter release at nerve terminals.
Original research paper: Nature Neurosci. 7, 613 – 620, (2004) |
 | Structural biology: Not so crystal clear
Protein structures solved by X-ray crystallography might not be as accurate as originally thought.
Original research paper: Structure 12, 831 – 838, (2004) |
 | Building Protein Microarrays On the Spot
NAPPA is an alternative approach to microarray proteomics, which may soon be used for the study of small molecule-protein interactions, identifying binding targets for individual compounds.
Original research paper: Science 305, 86 – 90, (2004) |
 | Lysophosphatidic acid: Signaling pain
Activation of the G-protein-coupled lysophosphatidic acid receptor (LPA1) and the Rho-ROCK pathway is required for the initiation and development of neuropathic pain.
Original research paper: Nature Medicine 10, 712 – 718, (July 2004) |
 | Signalling: Orphans find a family
Citric acid cycle intermediates can act as ligands for orphan G-protein-coupled receptors.
Original research paper: Nature 429, 188 – 193, (2004) |
 | T-cell responses: Cutting out the middle man
Toll-like receptor ligands directly promote activated CD4+ T-cell survival.
Original research paper: J. Immunol. 172, 6065 – 6073, (2004) |
 | Insect immunity: Distinct recognition
Lipopolysaccharide cannot stimulate the Immune-deficiency pathway, whereas polymeric and monomeric Gram-negative peptidoglycan can.
Original research paper: Immunity 20, 637 – 649, (2004) |
 | Diagnosis: Time for a change
The ERBB2 status of tumors has generally been considered to be stable, but a study shows that expression levels can change throughout disease progression.
Original research paper: Proc. Natl Acad. Sci 101, 9393 – 9398, (2004) |
 | Developmental biology: Integrating signals
Researchers reveal what happens when the BMP and MAPK signaling pathways – which are integrated at the level of their intracellular transducer, SMAD1 – are uncoupled in vivo.
Original research paper: Genes Dev. 18, 1482 – 1494, (2004) |
 | Ion channels: Crystal-clear interactions
Three papers have disclosed the atomic structure of the interacting domains between a- and ß-subunits of voltage-gated calcium channels, challenging some previous ideas about the workings of the channel.
Original research paper: Nature 429, 617 – 675, (2004) |
 | Cell cycle: It's a Smad world
Smad3 and CDKs play antagonistic roles in G1 progression, and in the absence of a strong TGF-ß signal, CDK phosphorylation of Smad3 can block its activity and allow cell cycle progression.
Original research paper: Nature 430, 226 – 231, (8 July 2004) |
 | Signalling: Making waves
Rab5 is a signaling GTPase involved in actin remodelling by receptor tyrosine kinases.
Original research paper: Nature 429, 309 – 314, (2004) |
 | Immune regulation: Instructing TH1/TH2-cell differentiation
The development of T helper 2 cells is not just a default pathway that occurs in the absence of TH1-cell-inducing signals but is an instructive process determined by Notch ligands.
Original research paper: Cell 117, 515 – 526, (2004) |
 | Tumour suppressors: Discrimination
E2F1 and E2F3a have a role in triggering the ARF-p53 tumor-surveillance pathway, and E2F3 has a role in maintaining this pathway in a repressed state during the normal cell cycle.
Original research paper: Genes Dev. 18, 1413 – 1422, (2004) |
 | Cardioprotection: All roads lead to GSK-3ß
Many cardioprotective drugs converge on the enzyme glycogen synthase kinase-3ß, indicating that the inhibition of this enzyme might be a good target to endow cardioprotection.
Original research paper: J. Clin. Invest. 113, 1535 – 1549, (2004) |
 | Accentuate the Negative
Selection-subtraction approach (SSA) is a universal genetic screening technique that enables negative selection.
Original research paper: Proc. Natl. Acad. Sci., USA. 101, 9327 – 9332 , (2004) |
 | Putting c-Fyn on a pedestal
Diarrhoea inducing enteropathogenic Escherichia coli (EPEC) subvert the host cell actin polymerization machinery to form 'pedestal-like' pseudopods, which are required for bacterial adherence and pathogenesis. This process is known to require the bacterial virulence factor Tir and now Vassilis Koronakis and colleagues show that the cellular tyrosine kinase c-Fyn phosphorylates Tir, leading to the recruitment of the Nck adaptor which triggers actin polymerization.
Original research paper: Nature Cell Biology 6, 618 – 625, (July 2004) |
 | Cytoskeleton: A new pathway to explore
c-Abl phosphorylates Dok1 to promote filopodia during cell spreading.
Original research paper: J. Cell Biol. 165, 493 – 503, (2004) |
 | Cell Adhesion: Spread the word
RNA and RNA binding proteins participate in early stages of cell spreading through spreading initiation centers.
Original research paper: Cell 117, 649 – 662, (2004) |
 | Tolerance: The 'indifferent' thief
CD8+ T cells maintain tolerance to myelin basic protein by 'epitope theft'.
Original research paper: Nature Immunol. 5, 606 – 614, (2004) |
 | Tumour suppressors: Happy couple
The interaction between p73 and the promyelocytic leukaemia (PML) gene product might be an important aspect of tumor suppression.
Original research paper: J. Exp. Med. 199, 1545 – 1557, (2004) |
 | Development: Put a lid on it!
The LIM homeodomain transcription factor Lmx1a is both necessary and sufficient to induce roof plate formation.
Original research paper: Development 131, 2693 – 2705, (2004) |
 | Kinases: Overcoming inhibition
Researchers describe a conserved structural determinant that governs the sensitivity of protein kinases to inhibition by small molecules.
Original research paper: Chem. Biol. 11, 691 – 701, (2004) |
