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.
 | Antiangiogenesis: Dll4 is a notch above VEGF
Blocking Delta-like ligand 4 (Dll4) results in increased but dysfunctional tumor vascularization, opening up a new avenue for antiangiogenenic cancer therapy.
Original research paper: Nature 444, 1032-1037, (2006) |
 | Osteoclast signaling: CaMKIV-CREB closes RANK
The Calmodulin-dependent kinase IV and cAMP-dependent response element binding protein (CaMK-CREB) pathway regulates the maturation and activation of osteoclasts.
Original research paper: Nature Medicine 12, 1410-1416 (2006) |
 | FGF signaling: Ligand specificity uncovered
The membrane protein Klotho directly binds fibroblast growth factor 23 (FGF23) and determines the ligand specificity of FGF receptor 1 (FGFR1).
Original research paper: Nature 444, 770-774 (2006) |
 | Dpp signaling: Mad degradation by eIF4A
The translation factor eIF4A regulates decapentaplagic (Dpp) signaling by inducing the degradation of the activated Smad transcription factor complex during Drosophila development.
Original research paper: Nature Cell Biology 8, 1407-1414 (2006) |
 | Contract and move
The activated Rho-ROCK-MLC2 signaling pathway generates contractile forces at distinct subcellular locations through endosomal trafficking.
Original research paper: J. Cell Biol. 175, 337 – 347, (2006) |
 | A dramatic way to remodel
New structural studies show how the dramatic conformational changes that occur during the Hsp90 reaction cycle might be coupled to client-protein remodeling.
Original research paper: Cell 127, 329 – 340, (2006) |
 | In brief: December 2006
Apoptosis | Development | Signal transduction | Sumoylation | Immune responses | T-cell signaling | Thymocyte development | Cell death | Tumor suppression | Tumor development | Signaling | Development | Synaptogenesis | Development | Cancer | Toxins |
 | Independent partners
A new model of planar cell polarity (PCP) in Drosophila has been proposed, in which the Dachsous/Fat and Starry night/Frizzled molecule systems act independently to polarize cells.
Original research paper: Development 133, 4561 – 4572, (2006) |
 | RIG-I reveals its perfect partner
The cytoplasmic RNA helicase retinoic-acid-inducible protein I (RIG-I) uses 5'-triphosphate RNA, and not viral replication or the formation of double-stranded (ds)RNA to discriminate between self and non-self RNAs.
Original research papers: Science 314, 997 - 1001 (2006); Science 314, 994 - 997 (2006) |
 | Leukaemia stem cells: More frequent and more mature
Leukemic stem cells (LSCs) in mouse MLL-AF9 acute myeloid leukemia (AML) are downstream myeloid lineage cells that have acquired the ability to ectopically self-renew, and survive and proliferate through an increased sensitivity to microenvironmental signals.
Original research paper: Cancer Cell 10, 257 – 268, (2006) |
 | Shootin 1 for the axon
The novel protein shootin 1 has an important role in determining which branch from a developing neuron outgrows the others to become an axon.
Original research paper: J. Cell Biol. 175, 147 – 157, (2006) |
 | The silenced synapse
The novel protein otoferlin is an essential component of sensory inner hair cells (IHCs) that controls immediate neurotransmitter exocytosis in response to IHC depolarization.
Original research paper: Cell 127, 277 – 289, (2006) |
 | Balancing bodily functions
Fos translation is inhibited by MiR-7b — a microRNA up-regulated in the hypothalamus after chronic hyperosmolar stimulation — thus maintaining the body's osmolarity equilibrium.
Original research paper: Proc. Natl Acad. Sci. USA 103, 15669 – 15674, (2006) |
 | Getting to the root of relapse
Targeting CD44 with the monoclonal antibody H90 can interfere with the anchoring of leukemic stem cells (LSCs) and prompt them to differentiate, causing them to lose their cancer-repopulating capacity.
Original research paper: Nature Med. 12, 1167 – 1174, (2006) |
 | Six degrees of separation
A new resource allows researchers to match the gene-expression signature of their system of interest to that of well-characterized chemical compounds-a hypothesis-generation tool with a bright future.
Original research paper: Cancer Cell 10, 321 – 330, (2006) |
 | Overcoming protein diversity on arrays
Researchers show that to reliably establish protein interaction networks from microarray data it is necessary to measure saturation binding curves for each arrayed protein and its potential binding partners.
Original research paper: J. Am. Chem. Soc. 128, 13668 – 13669, (2006) |
 | DNA damage: The road of death
CDK2-mediated phosphorylation of the transcription factor FOXO1 regulates apoptosis following DNA damage, linking DNA damage to apoptosis.
Original research paper: Science 314, 294 – 297, (2006) |
 | The potential of networking
A map of the ES-cell interactome - a network dedicated to establishing and maintaining pluripotency - has been constructed by identifying proteins that interact with Nanog.
Original research paper: Nature (2006) |
 | Mutual appreciation
A myeloid-cell-specific, activation-induced C-type lectin has been identified as a ligand for the human natural killer (NK)-cell activating receptor NKp80, thus enabling the mutual activation of NK and myeloid cells.
Original research paper: Nature Immunol. 7, 1334 - 1342 (2006) |
 | Expanding the pathway
Studies now show that the Salvador-Warts-Hippo pathway can respond to extracellular signaling through the atypical cadherin Fat, stressing the importance of this pathway in tumorigenesis.
Original research paper: Curr. Biol. (2006) |
 | The dawn of Neanderthal genomics
By studying the Neanderthal genome sequence it has been estimated that approximately 8% of human lineage DNA sequence changes have occurred after divergence from the Neanderthal.
Original research paper: Science 314, 1113 – 1118, (2006) |
 | GEF a move on!
A new study sheds light on the specificity of the GEF (guanine-exchange factor) complex TRAPP for different Rab GTPases and thus, the regulation of membrane traffic flow.
Original research paper: Nature Cell Biol. 8, 1263 – 1269, (2006) |
 | Another roll of the Dice(r)
The ribonuclease III enzyme Dicer is required for CD4+CD25+ regulatory T (TReg) cell development and for the efficient induction of transcription factor forkhead box P3 (FOXP3) expression by transforming growth factor ß (TGFß).
Original research paper: J. Exp. Med. (2006) |
 | Intricate insights
Studies in mouse models of pancreatic carcinogenesis indicate that the loss of Tgfbr2 or Smad4 can induce different effects on tumor development and progression.
Original research paper: Genes Dev. (2006) |
 | Imprinting links embryogenesis and tumor formation
Researchers have identified a network of imprinted genes that are involved in the control of embryonic growth, and potentially in tumor development.
Original research paper: Dev. Cell 11, 711 – 722, (2006) |
 | Making connections through MeCP2
Phosphorylation of the transcriptional repressor MeCP2 regulates dendritic patterning, spine morphogenesis and activity-dependent induction of Bdnf transcription.
Original research paper: Neuron 52, 255 – 269, (2006) |
 | SIMS for membranes
By combining two imaging methods researchers are able to investigate membrane complexity and lipid distribution at high spatial resolution.
Original research paper: Nat. Methods 3, 1007 – 1012, (2006) |
 | Even receptors get stressed
Mechanical stress across the plasma membrane of endothelial cells can directly activate G-protein-coupled receptors.
Original research paper: Proc. Natl Acad. Sci. USA 103, 15463 – 15468, (2006) |
 | BRCA1 — keeping excessive activities in check
A new function of BRCA1 in the assembly of the mitotic spindle has been uncovered, which might be relevant to BRCA1-mediated tumor suppression.
Original research paper: Cell 127, 539 – 552, (2006) |
 | Bringing the outside in
The machinery for endoplasmic reticulum (ER) protein retrotranslocation operates in the phagosomes of dendritic cells and is responsible for the transfer of exogenous antigens into the cytosol for cross-presentation.
Original research paper: Immunity 25, 607 – 617, (2006) |
 | Viral persistence: IL-10 is the key
Elevated interleukin-10 (IL-10) production causes the immunosuppression that allows viruses to persist unchecked by the immune system.
Original research paper: J. Exp. Med. (2006) |
 | Body building is about teamwork
The tumor suppressor family members p53, p63 and p73 act synergistically on the retinoblastoma protein (RB) during myogenic differentiation and their loss of function promotes malignant transformation.
Original research paper: Cancer Cell 10, 281 – 293, (2006) |
