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.
 | Neuroscience: Fear is sent PAKing
The Rac1–Cdk5 signaling pathway regulates the learned response to fear by modulating the activity of the PAK1 serine/threonine kinase.
Original research paper: Nature Neuroscience 10, 1012-1019 (2007) |
 | Tumor suppression: p15Ink4b joins the club
A potent tumor suppressor role for the cyclin dependent kinase inhibitor p15INK4b is uncovered in INK4a-null cells.
Original research paper: Nature 448, 943-946 (2007) |
 | Lymphoma cells: Hedging against apoptosis
Hedgehog signaling protects lymphoma cells against apoptosis by upregulating Bcl-2.
Original research paper: Nat. Medicine 13, 944-951 (2007) |
 | Lung cancer: LKB1 loss poses a triple threat
The combination of an oncogenic mutation in Ras and the loss of the tumor suppressor protein LKB1 promotes aggressive, metastatic non-small cell lung cancer through an Ink4a/Arf- and p53-independent pathway.
Original research paper: Nature 448, 807-810 (2007) |
 | Ras signaling: A digital-to-analog converter
Nanoclusters of Ras–mitogen activated protein kinase (MAPK) signaling molecules in the plasma membrane convert binary Erk activation into an overall graded response to stimuli, affording exquisite sensitivity to upstream pathway activation.
Original research paper: Nature Cell Biology 9, 905-914 (2007) |
 | Regulatory T cells: Reciprocal regulation by retinoic acid
The vitamin A metabolite retinoic acid is a key regulator of transforming growth factor β (TGFβ)-mediated differentiation of regulatory T cells and T helper 17 (TH17) cells.
Original research paper: Science 317, 256–260 (2007) |
 | Microenvironment: A disturbed background
Genetic deletion of retinoblastoma (RB) or retinoic acid receptor gamma (Rarg) alters the bone marrow microenvironment, which promotes differentiation of hematopoetic stem cells and predisposes null mice to myeloproliferative disorders.
Original research paper: Cell 129, 1081–1095 (2007) |
 | In brief: August 2007
T helper cells | Innate immunity | T cells | Structure | Immunogenetics | Tumorigenesis | Resistance | Genetics | RNA world | Genome instability | Pain | Synapse assembly | Addiction | Neurodegenerative diseases | Endocannabinoids | Biophysics |
 | Signalling: Expression levels are not as they appear
The tyrosine kinase Src might promote oncogenesis in estrogen receptor α (Erα-) breast cancers by inducing degradation of ERα, establishing Src as a potential anti-cancer therapy target in ER- breast cancer.
Original research paper: J. Clin. Invest. 117, 2205–2215 (2007) |
 | Development: Alternative splicing switches on the brain
The polypyrimidine tract binding protein (PTB) alters the assembly of the spliceosome to repress the splicing of certain alternative exons, which affects neuronal differentiation.
Original research paper: Genes Dev. 21, 1636–1652 (2007) |
 | Drug techniques: siRNA: brain delivery breakthrough
A new technique enables the targeted delivery of small interfering RNA (siRNA) molecules across the blood brain barrier to the central nervous system, permitting gene-by-gene analysis of brain function and validation of therapeutic targets.
Original research paper: Nature 448, 39–43 (2007) |
 | Glia: It's a wrap
The ability of the small GTPase Rac1 to induce actin reorganization and lamellipodia formation is critical for radial axon sorting, the process by which Schwann cells form contacts with and myelinate axons.
Original research paper: J. Cell Biol. 177, 1051–1061 (2007) |
 | Bacterial secretion: Post-translational control for secretion
Threonine phosphorylation and dephosphorylation elegantly regulate the assembly and function of the type VI secretion system of Pseudomonas aeruginosa.
Original research paper: Nature Cell Biol. 9, 797–803 (2007) |
 | Mechanisms of disease: A spate of RAB8
Two separate studies link RAB8 to two different human diseases — microvillus inclusion disease and Bardet–Biedl syndrome (BBS) — and highlight the physiological importance of protein trafficking.
Original research paper: Nature 448, 366–369 (2007) |
 | Lymphocyte development: Damage limitation
The kinase ataxia–telangiectasia mutated (ATM) has a crucial role in maintaining genomic stability by activating cell-cycle checkpoints in response to DNA damage.
Original research paper: Cell 130, 63–75 (2007) |
 | Breast cancer: X-linked tumour suppression
FOXP3, a member of the forkhead/winged-helix family of transcription factors, has been identified as an X-linked suppressor of breast cancer that inhibits tumorigenesis by repressing expression of the oncogene ERBB2 (also known as HER2).
Original research paper: Cell 129, 1275–1286 (2007) |
 | Tumorigenesis: Innate response
MYD88 is a crucial component of tumorigenesis in tissues that are subject to heightened or disrupted tissue repair and/or renewal pathways, further re-enforcing the link between tissue repair and oncogenesis.
Original research paper: Science 317, 121–124 (2007) |
 | Neurodegenerative diseases: Age concerns
Two studies have provided links between ageing-related changes in neurons and the development of Parkinson's disease.
Original research paper: Nature 447, 1081–1086 (2007) |
 | Osteoporosis: Building up the bone
The proline-rich tyrosine kinase 2 (PYK2) — a member of the focal adhesion kinase family — plays a key role in the regulation of bone formation; thus, inhibitors of this kinase might represent potential bone-building therapies for osteoporotic disease.
Original research paper: Proc. Natl Acad. Sci. USA 104, 10619–10624 (2007) |
 | Bioinformatics: Training a computer's eye on cell shape
To map the signaling networks that regulate cell morphology, researchers have developed a method to quantify cell shape and integrate the resulting data to construct networks.
Original research paper: Science 316, 1753–1756 (2007) |
 | Post-translational modification: UBE1, you're not alone
Contrary to previous assumptions, researchers have now found a second ubiquitin E1 activating enzyme that defines a separate ubiquitin-conjugating pathway.
Original research paper: Nature 447, 1135–1138 (2007) |
 | Post-translational modification: It doesn't take three
Monoubiquitylation of ubiquitin-binding domain-containing substrates has now been shown to also occur in the absence of ubiquitin E3 ligase activity.
Original research paper: Mol. Cell 26, 891–898 (2007) |
 | Immune regulation: New player in the generation of TH17 cells
The cytokine interleukin-21 (IL-21) is not only produced by TH17 cells but is also a potent and necessary inducer of TH17-cell differentiation.
Original research paper: Nature 448, 480–483 (2007) |
 | Metabolic diseases: A shared target
Inhibiting the adipocyte fatty-acid-binding protein Ap2 (also known as FABP4) — a protein known to integrate inflammatory and metabolic responses — may be a novel strategy for treating metabolic diseases.
Original research paper: Nature 447, 959–965 (2007) |
 | Angiogenesis: Hidden signatures written in blood
Several genes have been identified that are selectively upregulated only in tumor blood vessels and may provide specific targets for tumor angiogenesis.
Original research paper: Cancer Cell 11, 539–554 (2007) |
 | Neurogenesis: New neurons in a whiff
In female mice neurogenesis is stimulated by exposure to pheromones from dominant males, which can lead to alterations in social memory and reproductive behavior.
Original research paper: Nature Neurosci. 10, 1003–1011 (2007) |
 | Cell division: Protection for cyclists
Activation of the unfolded protein response (UPR) is required for efficient cytokinesis, highlighting a feedback mechanism between cell division and endoplasmic reticulum (ER) stress.
Original research paper: J. Cell Biol. 177, 1017–1027 (2007) |
 | Mucosal immunology: APRIL drives switch to IgA2
The T-cell receptor-stimulated release of APRIL (a proliferation-inducing ligand) by intestinal epithelial cells promotes IgA class switching and protection from microbes.
Original research paper: Immunity 26, 812–826 (2007) |
 | Chromatin: A blast of HOTAIR silences distant chromatin
Non-coding RNAs that are transcribed from one of the four homeotic (Hox) loci function in trans to repress a Hox gene cluster on a different chromosome.
Original research paper: Cell 129, 1311–1323 (2007) |
 | Synaptogenesis: Selective stabilization
The postsynaptic transmembrane neuroligins NL-1 and -2 have opposite roles in synaptic stabilization; NL-1 supports excitatory synapses, while NL-2 increases the number of inhibitory synapses.
Original research paper: Neuron 54, 919–931 (2007) |
 | Chemical biology: Rapamycin to the rescue!
A new strategy exploits protein ubiquitination in a three-hybrid assay to modulate protein expression with exquisite sensitivity and specificity.
Original research paper: Proc. Natl. Acad. Sci. USA 104, 11209–11214 (2007) |
 | Cell signalling: The power of NetworKIN
The new computational approach NetworKIN combines consensus sequence motifs and protein-association networks to predict which protein kinases target experimentally identified phosphorylation sites in vivo.
Original research paper: Cell 129, 1415–1426 (2007) |
 | Immune tolerance: New mechanism of tolerance induction in cancer
Myeloid-derived suppressor cells induce CD8+ T-cell tolerance to tumors by blocking peptide–MHC–TCR (T-cell receptor) binding through the nitration of the TCR–CD8 complex.
Original research paper: Nature Med. 13, 828–835 (2007) |
 | Breast cancer: A useful combination
Using a combination of genomic and functional analyses, IKBKE (inhibitor of  B kinase  ) has been identified as a novel breast cancer oncogene whose overexpression activates nuclear factor B.
Original research paper: Cell 129, 1065–1079 (2007) |
 | Targeting: Intra-fering with interactions
The intrabody — an antibody fragment that can be expressed within a cell — iDab#6 binds to the oncogenic Ras variant HRAS–G12V and inhibits Ras-dependent tumorigenesis and metastasis.
Original research paper: EMBO 26, 3250–3259 (2007) |
 | Neuropeptides: Orexin neurons on acid
Orexin-producing neurons act as chemosensors of extracellular H+ and CO2 levels and thus might play a part in the homeostatic regulation of breathing.
Original research paper: Proc. Natl Acad. Sci. 104, 10685–10690 (2007) |
 | Neurodegenerative diseases: Channel switch rejuvenates neurons
Parkinson disease progression in dopaminergic neurons of the brain's substantia nigra pars compacta (SNc) region can be avoided by blocking their Ca2+ channels.
Original research paper: Nature 447, 1081–1086 (2007) |
