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.
 | Myeloproliferative disorders: Beware of Jak2 tyrosine kinase
A single amino-acid substitution in the Jak2 tyrosine kinase renders it constitutively active and causes several hematopoietic stem cell malignancies.
Original research paper: Nature 434, 1144 – 1148, (28 April 2005) |
 | Development:
Youth is overrated
Regenerating cells in Drosophila melanogaster imaginal discs seem to have a unique cell cycle profile with characteristics of both younger and older cells, which challenges the conventional view of rejuvenation.
Original research paper: Cell 120, 383 – 393, (2005) |
 | In brief: April 2005
DNA repair | Chromosome segregation | Plant biology | Innate immunity | Viral immunity | T-cell responses | B-cell development | Natural killer cells | RNA world | Technology | Technology | Developmental genetics | Human disease | Functional genomics | Cardiovascular disease | Kinases | Imaging and Visualization | Proteomics | RNA Interference | Microbiology |
 | Apoptosis:
Fragments of death
Mitochondrial fragmentation — previously thought to be an exclusive characteristic of apoptotic mammalian cells — is also a feature of apoptosis in C. elegans.
Original research paper: Nature 433, 754 – 760, (2005) |
 | Inflammation:
D6 clears away inflammatory chemokines
The chemokine receptor D6 appears to be involved in clearing β-chemokines from inflamed skin and therefore in resolving inflammation.
Original research paper: Nature Immunol. 6, 403 – 411, (2005) |
 | Metastasis:
A fish by any other name...
The Src substrate TKS5/FISH — a scaffold known to localize to podosomes in transformed cells — now has a role in podosome formation, extracellular-matrix degradation and the invasive behavior of some human cancer cells.
Original research paper: Cancer Cell 7, 155 – 165, (2005) |
 | Neuronal migration:
Reelin out the hindbrain nuclei
The extracellular matrix protein reelin (RELN) — best known for regulating the radial migration of neurons in the developing neocortex — appears to be required in the hindbrain, where it controls a specific step in the positioning of certain motor nuclei.
Original research paper: Development 132, 1175 – 1185, (2005) |
 | G-protein-coupled receptors:
Setting traps for drug discovery
A technique for 'trapping' small molecular fragments at the proposed binding site of a G-protein-coupled receptor (GPCR) reveals clues to receptor activation.
Original research paper: Proc. Natl Acad. Sci. USA 102, 2719 – 2724, (2005) |
 | A need for speed
A new target-immobilized NMR technique for screening binding interactions greatly reduces the required target quantity and experimental time.
Original research paper: Chem. Biol. 12, 207 – 216, (2005) |
 | Viral pathogenesis: Preserving the message
New light has been shed on the mechanism that leads to the overproduction of cytokines by cells that are infected with Kaposi's sarcoma-associated herpesvirus (KSHV), implicating the mitogen-activated protein kinase (MAPK)-associated protein kinase-2 (MK2).
Original research paper: Science 307, 739 – 741, (2005) |
 | Modelling synapses: Excited over LAR
LAR receptor tyrosine phosphatases are required for the development and maintenance of excitatory synapses, partly by regulating the dendritic targeting of cadherin–β-catenin complexes.
Original research paper: Nature Neuroscience 8, 458 – 467, (2005) |
 | Signalling:
Reassessing Ras routes
The specific compartmentalized localization and activity of the different Ras isoforms appears to be maintained through a constitutive de- and re-palmitoylation cycle.
Original research paper: Science 4, 373 – 385, (11 Feb 2005) |
 | Epigenetics: RB1 goes global
Retinoblastoma 1 (RB1) is not just a transcriptional repressor protein, but is also required for the assembly of constitutive heterochromatin.
Original research paper: Nature Cell Biol. 7, 420 – 428, (2005) |
 | T-cell development:
Committing to the CD4 lineage
The transcription factor T-helper-inducing POZ/Krüppel-like factor (Th-POK) has just been characterized as the central regulator of one of the key decisions in T-cell development — the CD4/CD8 lineage choice.
Original research paper: Nature 433, 826 – 833, (2005) |
 | Leukaemia:
Fusion cooking
The multi-step fusion process of mixed lineage leukaemia (MLL) proteins, which occurs during leukemogenesis, involves fusion partners such as the septin SEPT6.
Original research paper: J. Clinical Invest. 115, 919 – 929, (2005) |
 | Melanoma:
Stripey surrogates
Research in zebrafish has revealed that the serine/threonine kinase BRAF interacts genetically with the p53 pathway to cause melanomas.
Original research paper: Curr. Biol. 15, 249 – 254, (2005) |
 | Neurogenesis:
Reverse to proliferation
A new mechanism that negatively regulates the number of neurons in the adult brain has just been identified, and involves EphA7-induced ephrin-A2 reverse signaling in neural progenitors.
Original research paper: Genes Dev. 19, 462 – 471, (2005) |
 | Nuclear receptors:
Choosing the right path
A new compound modulates inflammation via oestrogen receptor pathway-selective signaling.
Original research paper: Proc. Natl Acad. Sci. USA 102, 2543 – 2548, (2005) |
 | Bubbles without toil or trouble
A new technique permits the rapid generation of submicrometer-sized vesicles from mammalian cells, which recreate the membrane and cytoplasmic environment of the parent cell, potentially enabling a broad range of nanoscale cellular screens.
Original research paper: J. Am. Chem. Soc. 127, 2908 – 2912, (2005) |
 | TCR signaling: a shortcut to p38 MAPK activation
T cell signaling reveals an alternative pathway for p38 MAPK activation, controlled by the tyrosine kinase Zap70 and Gadd45α.
Original research paper: Nature Immunology 6, 390 – 395, (2005) |
 | Development:
Controlling the spread
Shifted (Shf) is a newly characterized secreted protein that is required to control the movement of the morphogen Hedgehog (Hh) in Drosophila melanogaster.
Original research paper: Dev. Cell 8, 241 – 253, (2005) |
 | Membrane trafficking:
Controlling the flow
Characterization of the golgin-84 protein has shown that it tethers to CASP-binding COPI vesicles and joins its family members in defining subpopulations of COPI vesicles.
Original research paper: Science 307, 1095 – 1098, (2005) |
 | T-Cell responses:
Function and partner found for orphan SIRP-β2
The binding of the signal-regulatory protein (SIRP) family member SIRP-β2 to CD47 regulates T-cell adhesion to antigen-presenting cells (APCs) and co-stimulates T-cell proliferation.
Original research paper: Blood 105, 2421 – 2427, (2005) |
 | T-cell responses:
Too fat to respond
The lipid mediator sphingosine 1-phosphate (S1P), recently recognized to be a new type of chemotactic signal for T cells, is also important for the effector responses of mature T cells.
Original research paper: J. Immunol. 174, 2485 – 2488, (2005) |
 | Metastasis:
Moving PARts
Cancer cells use matrix metalloproteinase 1 (MMP1) to cleave and activate the G-protein-coupled receptor protease-activated receptor 1 (PAR1) and invade surrounding stromal tissues.
Original research paper: Cell 120, 303 – 313, (2005) |
 | Breast cancer:
Small size, big potential
A recent analysis of the stucture and functional interactions of human liver-receptor homolog 1(LRH1) has identified this protein as a possible target for small-molecule inhibitors that could potentially slow the progression of hormone-sensitive breast cancer.
Original research paper: Nature Struct. Mol. Biol. 12, 357 – 363, (2005) |
 | Neurodegenerative disease:
ALS meets RNAi
RNA interference (RNAi) has been used successfully to interfere with the progression of pathology in an animal model of amyotrophic lateral sclerosis (ALS) — a fatal neurodegenerative disease that attacks both upper and lower motor neurons.
Original research paper: Nature Med. 2, 806 – 819, (13 March 2005) |
 | Kinase inhibitors:
Surveying the kinome
A quick, sensitive screen for identifying the binding preferences of protein kinases for various compounds has made it possible to assemble detailed interaction maps, with important implications for drug design.
Original research paper: Nature Biotechnol. 23, 329 – 336, (2005) |
 | The mighty micro
A computational prediction method analyzing the binding of microRNAs (miRNA) to their mRNA target sites shows that many Drosophila melanogaster genes are targets for miRNA regulation.
Original research paper: PLoS Biology 3, e85 – , (2005) |
 | Chemotaxis: PTEN moves to Rock n’ Rho beats
Rho GTPases regulate the localization and activation of the tumor suppressor phosphatase PTEN in leukocyte chemotaxis.
Original research paper: Nature Cell Biology 7, 399 – 404, (2005) |
 | Cell cycle:
Timed cyclin'
New research reveals that cyclins use different mechanisms to promote the phosphorylation of S-phase- and M-phase-specific cyclin-dependent kinase (CDK) substrates.
Original research paper: Nature 434, 104 – 108, (2005) |
 | Immune regulation:
NKT-cell defects in XLP
A deficiency in the adaptor protein SAP blocks the development of natural killer T (NKT) cells, which seems to contribute to the development of X-linked lymphoproliferative disease (XLP).
Original research paper: Nature Med. 11, 340 – 345, (2005) |
 | Thymic development:
TRAF6 distributes tolerance
The tumor-necrosis-factor receptor (TNFR)-associated factor 6 (TRAF6) appears to be required for the differentiation and organization of medullary thymic epithelial cells (mTECs) and for the induction of T-cell self-tolerance.
Original research paper: Science (10 Feb 2005) |
 | Developmental biology:
A model model system
Two new papers describe novel computational methods for modeling biological systems, including the mapping of signaling events during Caenorhabditis elegans vulva development and the gene expression pattern during Drosophila embryogenesis.
Original research paper: Proc. Natl Acad. Sci. USA 102, 1951 – 1956, (2005) |
 | Antiviral drugs:
Salubrious inhibition
Phosphatase inhibition could be a feasible therapeutic strategy against cell stress.
Original research paper: Science 307, 935 – 939, (2005) |
 | Test tubes go microscopic
Microscopic 'test tubes' have permitted researchers to accurately quantify the efficiency of single enzyme molecules.
Original research paper: Nat. Biotechnol. 23, 361 – 365, (2005) |
 | HIV: A step ahead of drug resistance
Blocking a host-cell factor — human deoxyhypusine synthase (DHS) — provides a successful means of preventing the replication of HIV-1and holds great promise for the development of antiretroviral therapies to treat this disease.
Original research paper: J. Clin. Invest. 115, 76 – 85, (2005) |
 | Hematopoietic stem cells : Notch and Wnt unite
Notch signaling is critically involved in the maintenance of a self-renewing hematopoietic stem cell pool, partly through the integration of Wnt signaling.
Original research paper: Nature Immunology 6, 314 – 322, ( 2005) |
 | Endocytosis:
Gaining independence
Two new endocytic pathways that are independent of both clathrin and caveolae have now been identified and characterized.
Original research paper: J. Cell Biol. 168, 465 – 476, (2005) |
 | Cytoskeleton:
Small changes, big response
Phosphatidylinositol 4,5- bisphosphate (PtdIns(4,5)P2) binds to neuronal WiskottAldrich syndrome protein (N-WASP) in a multivalent and cooperative manner, resulting in switch-like activation of N-WASP.
Original research paper: Mol. Cell 17, 181 – 191, (2005) |
 | Immune regulation:
Cellular collaborations
CD8α+ T cells and natural killer T (NKT) cells, in collaboration with mesenteric lymph node (MLN) B cells, have now been shown to protect mice from CD4+ T-cell-induced colitis.
Original research paper: Proc. Natl Acad. Sci. USA 102, 2010 – 2015, (2005) |
 | Sensory transduction:
Seeing the light
Melanopsin — a pigment that is found in the type of retinal ganglion cell that allows light to entrain the circadian clock — can also function as a photopigment in other types of cell.
Original research paper: Nature 433, 741 – 745, (2005) |
 | More than an atlas of the brain
The expression of mouse transcription factors in all major brain regions and in a variety of other tissues has now been mapped, unraveling a plethora of information.
Original research paper: Science 306, 2255 – 2257, (2004) |
