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.
 | Neuronal stem cells: Less Notch, more neurons
Epidermal growth factor-like domain 7 (EGFL7) antagonizes Notch signaling to limit neural stem cell self renewal and promote neurogenesis.
Original research paper: Nature Cell Biology advance online publication, 7 June 2009 (DOI 10.1038/ncb1896) |
 | Infectious disease: Mycobacteria set up cAMP in macrophages
Phagocytosed Mycobacterium tuberculosis produces a burst of cAMP in macrophages that subverts the host immune response.
Original research paper: Nature advance online publication, 10 June 2009 (DOI 10.1038/nature08123) |
 | Kinases: An activating inhibitor?
ATP-competitive inhibitors induce phosphorylation priming of the protein kinases Akt and PKC, suggesting that nucleotide binding, rather than intrinsic catalytic activity, stimulates kinase activation.
Original research paper: Nature Chemical Biology advance online publication, 24 May 2009 (DOI 10.1038/nchembio.183) |
 | Cancer: A tumor suppressor is DSCRibed on chromosome 21
The protein products of two genes on chromosome 21 — Dscr1 and Dyrk1a — suppress angiogenesis and inhibit tumor growth by antagonizing VEGF signaling.
Original research paper: Nature advance online publication, 20 May 2009 (DOI 10.1038/nature08062) |
 | In brief: June 2009
Mitosis | 2010 Protein degradation | Polycomb proteins | Neuroimmunology | Metabolism | Resistance | Stress | Anticancer drugs | High-throughput screening | Anticancer drugs | Chemical biology |
 | DNA repair: Time to switch
CTIP (also known as RBBP8) is a molecular switch that directs cells towards homologous recombination as they enter S phase, rather than more error-prone mechanisms of repairing DNA double-strand breaks.
Original research paper: Nature 459, 460-463 (2009) |
 | Therapy: FGFR3 is key
The growth of bladder cancer tumors that express mutant FGFR3 can be blocked by monoclonal antibodies targeting the mutant protein.
Original research paper: J. Clin. Invest. 119, 1216-1229 (2009) |
 | Chemical senses: Sniffing out disease
Formyl peptide receptor (FPR) gene family members that are expressed in sensory neurons in the vomeronasal organ can detect molecules related to disease or inflammation.
Original research paper: Nature 22 Apr 2009 (doi: 10.1038/nature08029) |
 | Stem cells: Micro-reprogramming
microRNA molecules can be used to generate induced pluripotent stem cells in the mouse without permanently modifying the genome.
Original research paper: Nat. Biotechnol. 27, 459-461 (2009) |
 | Cellular microbiology: Examining the Fic domain
Fic domain-containing proteins are a novel class of enzymes that can both mediate bacterial pathogenesis and add an AMP moiety to a conserved tyrosine residue in the switch I region of RhoA, Rac and Cdc42.
Original research paper: Mol. Cell 34, 93-103 (2009) |
 | Plant cell biology: New receptors for ABA
In plants, the pyrabactin resistance 1 (PYR1) and the PYR1-like (PYL) family of proteins are at the apex of a negative regulatory pathway that controls abscisic acid signaling by inhibiting type 2C protein phosphatases (PP2Cs).
Original research paper: Science 324, 1068-1071 (2009) |
 | T cell differentiation: The TH1 two step
TH1 cell differentiation is mediated by activation of a T-cell receptor (TCR)–IFNγ–T-bet signaling loop, followed by activation of an IL-12–T-bet signaling loop.
Original research paper: Immunity 30, 673-683 (2009) |
 | Prostate cancer: Resistance is (hopefully) futile
Three papers describe promising new ways in which the androgen receptor (AR) might be targeted to overcome resistance to anti-androgen therapy for prostate cancer.
Original research paper: Proc. Natl Acad. Sci. USA 106, 7233-7238 (2009) |
 | Genomics: A modular approach to signalling
Gene expression 'signatures' of oncogenic pathways can be used to predict disease outcome and response to therapeutics in cancer.
Original research paper: Mol. Cell 34, 104-114 (2009) |
 | Neurodegenerative disease: NURR1 puts a dampener on inflammation
The nuclear receptor NURR1 can suppress potentially neurotoxic inflammatory gene expression in microglia and astrocytes to protect dopaminergic neurons from inflammation-induced death.
Original research paper: Cell 137, 47-59 (2009) |
 | Antiviral immunity: IL-21: in it for the long run
IL-21 production by CD4+ T cells provides the necessary boost to support CD8+ T-cell responses during chronic viral infection.
Original research paper: Science 7 May 2009 (10.1126/science.1174182) |
 | Metastasis: Attack of the mutant p53
Mutant p53 and wild-type p63 have opposing roles in transforming growth factor β (TGFβ)-induced metastasis.
Original research paper: Cell 137, 87-98 (2009) |
 | Proteomics: Biomarkers on a nanoscale
The nanofluidic proteomic assay (NIA) separates proteins according to their individual isoelectric points — which change according to phosphorylation — and hence could be used to assess differences in signaling behavior and protein expression in tumors.
Original research paper: Nature Med. 15, 566-571 (2009) |
 | Neuronal migration: You have arrived
Upregulation of the K+-Cl- co-transporter KCC2 (also known as SLC12A5) induces changes in extracellular GABA levels, causing cortical interneurons to stop migrating.
Original research paper: Neuron 62, 53-71 (2009) |
 | Systems biology: A functional blueprint of E. coli
The integration of proteomics data with genomic-context analysis has permitted the development of a protein-function prediction tool to annotate functional orphans in Escherichia coli.
Original research paper: PLoS Biol. 7, e100096, (2009) |
 | Cell migration: Talin heads off
Cdk5-dependent phosphorylation of the talin head domain prevents its interaction with Smurf1 and subsequent degradation, thus increasing talin head stability and promoting migration.
Original research paper: Nature Cell Biol. 11, 624-630 (2009) |
 | Inflammation: Targeting TNF
Oral delivery can specifically target siRNA-loaded particles to macrophages, where they silence expression of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), a serine/threonine kinase that influences the expression of the pro-inflammatory cytokine tumor necrosis factor (TNF).
Original research paper: Nature 458, 1180-1184 (2009) |
 | Therapeutics: Selectively targeting turnover
Inhibition of NAE (NEDD8-activating enzyme) interferes with the ubiquitin–proteasome system (UPS) and induces regression of lung tumor xenografts.
Original research paper: Nature 458, 732-736 (2009) |
 | Tumour suppressors: Multi-tasking
Three papers show that retinoblastoma (Rb) possesses functions outside of its traditional role as an inhibitor of cell cycle progression.
Original research paper: Cancer Cell 15, 184-194 (2009) |
 | MicroRNA: Keeping an eye on cell death
The microRNA miR-24a negatively regulates caspase 9 and apoptosis protease-activating factor 1 (apaf1) and is required for normal eye morphogenesis in Xenopus.
Original research paper: Genes Dev. 23, 1046-1051 (2009) |
