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.
 | Protein-protein interaction networks: To party or date?
The yeast interactome exhibits organized modularity where a small proportion of proteins – the 'hubs' – interact with many partners. These hubs fall into one of two categories: 'party' hubs, which interact with most of their partners simultaneously, and 'date' hubs, which bind different partners at different locations and times.
Original research paper: Nature 430, 88 – 93, (01 July 2004) |
 | Cell cycle: Cycling is an E2Ffort
Cell-cycle timing can be controlled through negative regulation of E2F1 by cyclin-dependent kinases.
Original research paper: Cell 117, 253 – 264, (2004) |
 | In brief: June 2004
Cell death | Cell cycle | Protein modification | Structure | Signalling | Innate Immunity | Antigen Presentation | Metastasis | Therapeutics | Plant Genetics | Pharmacogenetics |
 | Telomeres: The long and the short of it
Rif1 and Rif2 may promote the nonextendible telomeric state in which telomere elongation is somehow blocked.
Original research paper: Cell 117, 323 – 335, (2004) |
 | Autoimmunity: The more the merrier
Homeostatic expansion of T cells during immune insufficiency generates autoimmunity.
Original research paper: Cell 117, 265 – 277, (2004) |
 | T-cell memory: If your name's not down, you're not coming in
CD8aa-mediated survival and differentiation of CD8 memory T-cell precursors.
Original research paper: Science 304, 590 – 593, (2004) |
 | Tumorigenesis:
Right place, wrong time
The IκB kinase-β (IKKβ) regulates FOXO3A access to the nucleus and, therefore, tumorigenesis.
Original research paper: Cell 117, 225 – 237, (2004) |
 | Human genetics: Narrowing down the candidates for asthma
The properties of GPRA as a G-protein-coupled receptor, which might be used by a novel ligand as part of a new signaling pathway in asthma, mean that it has potential as a possible drug target.
Original research paper: Science 304, 300 – 304, (2004) |
 | Neurophysiology: Keeping in synch in the LGN
Activation of a subtype of mGluR1a in the thalamus drives the generation of α- and θ-rhythms in vivo.
Original research paper: Neuron 42, 253 – 268, (2004) |
 | Ion channels: Counting CaMs at calcium channels
Research suggests that just one calmodulin (CaM) molecule is required to turn off a calcium channel.
Original research paper: Science 304, 432 – 435, (2004) |
 | Cell biology of the neuron: The long and short of GluR2 expression
GluR2 translation is inhibited by a polymorphic repeat sequence in the 5'-untranslated region (5'-UTR) of the transcript.
Original research paper: J. Neurosci. 24, 3489 – 3499, (2004) |
 | Protein biochemistry: Finding the Perfect Pair
A new assay for the generation and screening of fragmented proteins promises to considerably accelerate the process of developing novel split-protein sensors for the in vivo characterization of protein interaction.
Original research paper: Chem. Biol. 11, 681 – 689, (2004) |
 | Protein phosphatase 1 structure: How MYPT1 adds specificity
Substrate specificity of the Ser/Thr protein phosphastase 1 (PP1) is provided by regulatory subunits. The crystal structure of PP1 and myosin phosphatase targeting subunit (MYPT1) shows how the catalytic cleft of PP1 is reshaped to increase PP1's catalytic activity and specificity for myosin.
Original research paper: Nature 429, 780 – 784, (17 June 2004) |
 | Membrane trafficking: Bring it back
Role of the mammalian retromer in sorting of the cation—independent mannose 6—phosphate receptor.
Original research paper: J. Cell Biol. 165, 111 – 122, (2004) |
 | Innate immunity: Caspase-12: the long and the short of it
Differential modulation of endotoxin responsiveness by human caspase—12 polymorphisms.
Original research paper: Nature 429, 75 – 79, (2004) |
 | Imaging: Glowing success
Researchers have found a bioluminescent method of monitoring the in vivo efficacy of drugs designed to inhibit the cyclin-dependent kinase CDK2.
Original research paper: Nature Med. 10, 643 – 648, (2004) |
 | Targeted therapies: No longer in the dark
Two studies reveal why only some subsets of patients with cancer are sensitive to the anticancer agent gefitinib, a small-molecule inhibitor of EGFR.
Original research paper: N. Engl. J. Med. 350, 2129 – 2139, (2004) |
 | Gene regulation: microRNA, control yourself!
The action of ARGONAUTE1 in the miRNA pathway and its regulation by the miRNA pathway are crucial for plant development.
Original research paper: Genes Dev. 18, 1187 – 1197, (2004) |
 | Neurological disorders: Stimulating findings
Two teams show that the loss of NMDA—receptor function may underlie cognitive and neurological decline after head injury, rather than the hyperactivation of NMDA receptors, as previously thought.
Original research paper: Proc. Natl Acad. Sci. USA 101, 5117 – 5122, (2004) |
 | The Tags That Bind: A New Way to Label PTPs
A newly developed chemical probe could considerably simplify the process of determining changes in the activity of tyrosine phosphatase enzymes, both globally and for individual proteins within the cell.
Original research paper: Proc. Natl. Acad. Sci., U.S.A. 101, 7943 – 7948, (2004) |
 | PI3K/Akt signaling: TORmenting prostate cancer
Inhibition of mammalian target of rapamycin (mTOR) reverses Akt-dependent prostate intraepithelial neoplasia (PIN) in mice through the regulation of both apoptotic and HIF-1a-dependent pathways.
Original research paper: Nature Medicine 10, 594 – 601, (2004) |
 | Cell Death: Death by self-digestion
Regulation of an ATG7–beclin 1 program of autophagic cell death by caspase-8.
Original research paper: Science 304, 1500 – 1502, (2004) |
 | Innate immunity:
Destroying Tolls
A study has identified a novel mechanism for negative regulation of specific TLR-signaling pathways – TRIAD3A-regulated ubiquitin-dependent proteasome degradation.
Original research paper: Nature Immunol. (25 April 2004) |
 | Signalling: Filling in the blanks in NF-κB signalling
The ubiquitin ligase TRAF6 and the kinase TAK1 have important roles in mediating IKK activation by BCL-10 and MALT1.
Original research paper: Mol. Cell 14, 289 – 301, (2004) |
 | Targeted therapies:
Layers of necessity
Src kinases Lyn, Hck and Fgr are a requirement for BCR–ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia.
Original research paper: Nature Genet. 36, 453 – 461, (2004) |
 | Axon guidance: Making axons cross
Slit and Robo proteins have conserved roles in midline commissural axon guidance.
Original research paper: Neuron 42, 213 – 223, (2004) |
 | Metabolic syndrome: Two for the price of one
A drug that acts on both angiotensin receptors and PPAR-γ could be a first line of defence against the metabolic syndrome that commonly presages cardiovascular disease and type 2 diabetes.
Original research paper: Hypertension 43, 993 – 1002, (2004) |
 | Phage Display 'Loophole' Reveals Dye-Binding Peptides
A modified screen for identifying antigen-binding peptides offers new possibilities for the targeting of fluorescent dye-based labeling.
Original research paper: Chem. Biol. 11, 347 – 356, (2004) |
 | Putting A New Face on Protein-Protein Interactions
Computational redesign of protein-protein interaction specificity.
Original research paper: Nat Struct. Mol. Biol. 11, 371 – 379, (2004) |
 | Cardiac hypertrophy: Stretching to your heart's content
Mechanical stress directly activates the angiotension II (AII) type 1 (AT1) receptor independently of AII in the cardiac hypertrophy response.
Original research paper: Nature Cell Biology 6, 499 – 506, (2004) |
 | Cancer: Proteins perish under spotlight
Functional proteomic screens reveal an essential extracellular role for Hsp90a in cancer cell invasiveness.
Original research paper: Nature Cell Biol. 6, 507 – 514, (2004) |
 | Stem cells: Bend me, shape me...
Cell shape, cytoskeletal tension and RhoA—ROCK signaling regulate stem cell lineage commitment.
Original research paper: Dev. Cell 6, 483 – 495, (2004) |
 | HIV: Pulling out the stops
Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue.
Original research paper: J. Exp. Med. 199, 1065 – 1075, (2004) |
 | Lymphocyte Signalling: Lay your bets: 2–1 on NK and NKT cells
The transcription factor T-bet has a novel role as a regulator of the terminal differentiation of NK cells and Va14i NKT cells.
Original research paper: Immunity 20, 477 – 494, (2004) |
 | Pharmacodynamics: PET power
Imaging the pharmacodynamics of HER2 degradation in response to Hsp90 inhibitors.
Original research paper: Nature Biotechnol. 22, 701 – 706, (2004) |
 | Apoptosis: Profit and loss
Bim is a suppressor of Myc-induced mouse B-cell leukemia.
Original research paper: PNAS 101, 6164 – 6169, (2004) |
 | Sensory systems: Linking cadherin to hearing
Cadherin 23 is a component of the tip link in hair-cell stereocilia.
Original research paper: Nature 428, 950 – 955, (2004) |
