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.
 | GPCRs and blood clotting: An inside job
Lidija Covic and colleagues have investigated a novel means of blocking the thrombin-induced activation of PAR by using a targeted system that works on the intracellular side of the GPCR.
25 October 2002
Original research paper: Nature Medicine 8, 1161 - 1165, (October 2002) |
 | Nuclear transport:
Two-way traffic
The groups of Joan Massagué and Caroline Hill report new insights into the transport of Smads in and out of the nucleus.
25 October 2002
Original research paper: Mol. Cell 10, 271 - 282, (2002) |
 | In brief: October 2002
Cell signalling | Cell signalling | Genetic screening | Oncogenes | Oncogenes | Technology | Inflammatory diseases | Anticancer drugs |
 | Cellular cytotoxicity:
CTL self-defence
A new study indicates that cytotoxic lymphocytes release granule-derived cathepsin B on degranulation, which associates with the cell surface and protects these cells against perforin attack and self-destruction.
25 October 2002
Original research paper: J. Exp. Med. 196, 493 - 503, (2002) |
 | Techniques:
Welcome interference
Agami and colleagues, reporting in Cancer Cell, show that oncogenic KRAS can be specifically and stably inactivated through the use of a viral RNA interference vector.
25 October 2002
Original research paper: Cancer Cell 2, 229 - 241, (2002) |
 | Human genetics: Simplifying complexity
Aravinda Chakravarti and colleagues have carried out a multi-faceted study of a model complex disorder, Hirschsprung disease (HSCR), and reveal new evidence of a genetic interaction between the two main genes that underlie HSCR.
25 October 2002
Original research paper: Nature Genet. 32, 237 - 244, (2002) |
 | Therapeutic proteins:
High affinity good, lower affinity better
Scientists from the Massachussetts Institute of Technology and Amgen have used computer modeling and protein chemistry to engineer granulocyte colony-stimulating factor (GCSF) variants with lower receptor affinity that are as biologically potent as wild-type GCSF, but remain active for longer.
25 October 2002
Original research paper: Nature Biotechnol. 20, 908 - 913, (2002) |
 | Structure-based drug design:
Reiterating the point
Davies et al. show that structure-based development and iterative biological evaluation can be used to optimize a cyclin-dependent-kinase inhibitor rapidly, resulting in nanomolar potency that is 1,000-fold greater than the parent compound.
25 October 2002
Original research paper: Nature Struct. Biol. 43, 2797 - 2804, (2002 Oct) |
 | Looking for the needle in the p53 stack
Two papers in Nature have enriched the repertoire of targets for Pin-1 by demonstrating that DNA-damage-induced activation of the tumor suppressor p53 is mediated by Pin-1.
18 October 2002
Original research paper: Nature AOP, (2 October 2002) |
 | DNA repair: Small cause, large effect
The results of a new study underline the importance of the Mre11 complex in the homeostasis of proliferative tissues.
18 October 2002
Original research paper: Genes Dev 16, 2237 - 2251, (2002) |
 | Cell Adhesion: Promoting partnerships
James Nelson's group now propose a function for Rac in the kinetics and strengthening of E-cadherin-mediated cell–cell adhesion.
18 October 2002
Original research paper: Dev. Cell 3, 259 - 270, (2002) |
 | Autoimmunity: Mast cells make the connection
In a recent Science paper, Lee et al. propose that mast cells provide a cellular missing link.
18 October 2002
Original research paper: Science 297, 1689 - 1692, (2002) |
 | Signalling: Fuzzy logic
Philip Beachy and colleagues report that inhibitors of the Hedgehog signaling pathway induce regression of established tumors in preclinical models of medulloblastoma, revealing a new therapeutic approach for this aggressive cancer.
18 October 2002
Original research paper: Science 297, 1559 - 1561, (2002) |
 | Human Evolution: Two mutations worth a thousand words (or more)
A new study by Enard et al. in Nature suggests that two amino-acid mutations in one gene might have contributed greatly to the evolution of modern humans.
18 October 2002
Original research paper: Nature 418, 869 - 872, (2002) |
 | Neurodegeneration:
Autophagy lurks around lurcher
New data from Yue et al. broadens the functional repertoire of what are commonly regarded as ionotropic receptors, to encompass signaling pathways that involve protein–protein interactions.
18 October 2002
Original research paper: Neuron 35, 921 - 933, (2002) |
 | Neurodegenerative Diseases: Tying up loose ends
Lipton and colleagues show how two proposed mechanisms for nerve-cell death are intimately linked, and should therefore help to direct therapies aimed at treating neurological disorders
18 October 2002
Original research paper: Science 297, 1186 - 1190, (2002) |
 | Axon pathways: A Roundabout way to find the right route
Neurons generate axonal processes that must extend over significant distances — and just how they do this has now begun to be elucidated. Rhee et al. show that activating Roundabout (or Robo), by binding it to the repulsive guidance cue Slit, leads to the inhibition of N-cadherin-mediated cell adhesion.
11 October 2002
Original research paper: Nature Cell Biology 4, 798 - 805, (October 2002) |
 | Apoptosis: Cut to death
New work from Jean Wang and colleagues published in Nature Cell Biology shows that cleavage of retinoblastoma protein is required for apoptosis of certain tissues in response to specific death stimuli.
11 October 2002
Original research paper: Nature Cell Biol. 4, 757 - 765, (2002) |
 | Signalling: Initiation of pro-IL-1ß processing
In Molecular Cell, Jürg Tschopp's group describe a caspase-activating complex that they have named the 'inflammasome', consisting of caspase-1, caspase-5, PYCARD and NALP1, which is structurally homologous to the NOD proteins.
11 October 2002
Original research paper: Mol. Cell 10, 417 - 426, (2002) |
 | T-cell homeostasis: T-cell build-up and blockade
Rathmell and colleagues report in Nature Immunology that Bak and Bax deficiency disrupts the processes involved in T-cell development and homeostasis, and that T-cell development is inhibited by the accumulation of cells that would normally be deleted by pro-apoptotic Bcl-2-family members.
11 October 2002
Original research paper: Nature Immunology 6, 1389 - 1399, (3 September 2002) |
 | Tumour Suppressors: Mystery molecule
In Nature, Bardeesy et al. propose that loss of LKB1 in normal cells could result in the formation of benign tumors, whereas loss in advanced neoplasms could promote malignant progression.
11 October 2002
Original research paper: Nature 419, 162 - 167, (2002) |
 | Therapeutics: Self destruction
Steven Rosenberg and colleagues describe a new immunotherapy approach that replaces up to 90% of a patients' normal lymphocytes with activated tumor-specific ones, resulting in regression of metastatic melanoma.
11 October 2002
Original research paper: Science 2, 227 - 238, (19 Sept 2002) |
 | Cell biology of the neuron:
A raft of possibilities
Delling et al. show that an adhesion molecule can regulate the lipid-raft-dependent trafficking of an ion channel, possibly providing a new mechanism for controlling synaptic transmission.
11 October 2002
Original research paper: J. Neurosci. 22, 7154 - 7164, (2002) |
 | Ligands: Sorting good from bad
According to a study by Limbird and colleagues, the key to sorting out the physiological wheat from the chaff might be to characterize the physiological and behavioural responses in mouse models that are heterozygous for the receptor of interest.
11 October 2002
Original research paper: Proc. Natl Acad. Sci. USA 99, 12471 - 12476, (2002) |
 | Take a closer look at the sensory rhodopsin II-transducer complex
Valentin Gordelly and colleagues have succeeded in picturing the X-ray structure of the complex between N. pharaonis sensory rhodopsin II (SRII) and its receptor specific transducer, halobacterial transducer II (HtrII), at a 1.94Å resolution, providing the first atomic picture of how this complex interacts.
4 October 2002
Original research paper: Nature 419, 484 - 487, (3 October 2002) |
 | Apoptosis:
Death theory turned on its head
A report by Lazebnik's group in Science implies that both cytokine-induced and stress-induced modes of apoptosis can proceed through conceptually similar pathways.
4 October 2002
Original research paper: Science 297, 1352 - 1354, (2002) |
 | Chromosome biology: Make it accessible
New data reveal an interesting function for the chromatin-remodelling machinery in DNA replication.
4 October 2002
Original research paper: Nature 418, 994 - 998, (2002) |
 | Cell Proliferation: Dual control
Two genes have been identified that, when mutated, confer a selective advantage to cells. Might they be mutated in cancer cells?
4 October 2002
Original research paper: Cell 110, 467 - 478, (2002) |
 | Mouse Models: One step closer...
ATM protein kinase protects cells from DNA damage by phosphorylating and activating proteins such as p53. But is this ability impaired in ATM-SRI mutants?
4 October 2002
Original research paper: Nature Genet. 32, 185 - 190, (2002) |
 | Ion Channels:
ASIC-nal integrator
Reporting in The Journal of Physiology, Allen and Attwell show that ASICs might act as signal integrators, responding to a series of changes that ensue during episodes of ischaemia.
4 October 2002
Original research paper: J. Physiol. (Lond.) 543, 521 - 529, (2002) |
 | G-Protein-Coupled Receptors: Lipidated peptides: a therapeutic tool kit
Cell-penetrating lipidated peptides, known as pepducins, can be used as tools to delineate the physiological roles of GPCRs and determine the therapeutic value of blockade of a particular signaling pathway.
4 October 2002
Original research paper: Nature Med. 99, 643 - 648, (2002 Oct) |
