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.
 | Trpm5: The sweet taste of successful signaling
Perez et al. have found that Trpm5, the fifth member of the melastatin-related TRP channel subfamily, is coexpressed with taste signaling molecules such as α-gus, Gγ13, phospholipase C-ß2 and IP3R3, and that it is also selectively expressed in taste tissue. This indicates that Trpm5 may be a capacitative calcium entry channel.
29 November 2002
Original research paper: Nature Neuroscience 5, 1169 - 1176, (November 2002) |
 | Cell cycle: Divide and rule
Brian Dynlacht and colleagues report in Developmental Cell the identification of a new cyclin-dependent kinase substrate with a function in controlling the centrosome cell cycle.
29 November 2002
Original research paper: Dev. Cell 3, 339 - 350, (2002) |
 | In brief: November 2002
Signalling | Thymic development | Prostate cancer | Angiogenesis | Apoptosis | Anticancer drugs | G-protein-coupled receptors |
 | Apoptosis: Broader role for Bcl-2
Recent work published in Nature indicates that Bcl-2 can act independently of the apoptosome to regulate caspase activation.
29 November 2002
Original research paper: Nature 419, 634 - 637, (2002) |
 | T-Cell signalling: IL-7 fine-tunes T-cell homeostasis
Seddon and Zamoyska have shown that IL-7 can induce proliferation independently, and that the relative contribution of IL-7 signaling to TCR-induced proliferation fine-tunes the response to different conditions.
29 November 2002
Original research paper: J. Immunol. 169, 3752 - 3759, (2002) |
 | Telomerase: ALTernative pathways?
Both telomerase and ALT pathways result in the addition of telomeric sequence onto the ends of chromosomes, preventing crisis, and allowing cells to proliferate indefinitely. But ALT seems to occur less frequently than might be expected.
29 November 2002
Original research paper: Proc. Natl Acad. Sci. USA 99, 12606 - 12611, (2002) |
 | Protein structure: Folding forecast
A study by Simmerling, Strockbine and Roitberg in The Journal of the American Chemical Society shows that computer simulations could at last be used to predict the three-dimensional structure of a protein accurately.
29 November 2002
Original research paper: J. Am. Chem. Soc. 124, 11258 - 11259, (2002) |
 | Toll-like receptors: TIRAP it up
Akira et al. and Medzhitov et al. have used knockout mice to study the adaptor protein TIRAP's role in the TLR signaling cascade, and show that TIRAP is specific to TLR2 and TLR4.
22 November 2002
Original research paper: Nature 420, 324 - 329, (21 November 2002) |
 | Apoptosis: A dysfunctional harlequin
Susan Ackerman and co-workers describe a genetic model for neurodegeneration that is mediated by oxidative stress. And, in so doing, they highlight a vital role for a key pro-apoptotic molecule — the apoptosis-inducing factor — in neuronal survival.
22 November 2002
Original research paper: Nature 419, 367 - 374, (2002) |
 | Cancer: Filling the hole
A recent Cell paper shows that apoptosis is important in maintaining luminal space and that tumor cells must suppress apoptosis to successfully invade the lumen.
22 November 2002
Original research paper: Cell 111, 29 - 40, (2002) |
 | B-Cell signalling: Directing B-cell destiny
The glycosylphosphatidylinositol (GPI)-linked form of immunoglobulin D initiates cyclic-AMP-dependent signaling that promotes the differentiation of resting B cells to germinal-centre B cells.
22 November 2002
Original research paper: Nature Immunol. 3, 951 - 957, (2002) |
 | Tumour immunology: Disarming defences
Tumors might evade the immune response by secreting soluble MHC class-I-chain-related protein A, which downregulates expression of the receptor NKG2D on host immune cells, so impairing the anti-tumor response.
22 November 2002
Original research paper: Nature 419, 734 - 738, (2002) |
 | Developmental biology: A balancing act
Chen et al. and Shin et al. identify and characterize a new mouse homeobox gene, Hop, which, although unable to bind DNA, modulates cardiac-specific gene expression by interacting with known major players in cardiogenesis.
22 November 2002
Original research paper: Cell 110, 713 - 723, (2002) |
 | Lead generation: Alternative route
Writing in the Journal of the American Chemical Society, van Dongen et al. describe the application of an approach such as NMR to the discovery of high-quality hits for the human adipocyte fatty-acid binding protein FABP4, which is a potential target for type 2 diabetes.
22 November 2002
Original research paper: J. Am. Chem. Soc. 1, 211 - 219, (2002 Sep 12) |
 | Ad-ing AMPK to the problem: Obesity and diabetes
Yamauchi et al. show how AMPK is activated by the hormone adiponectin, thereby directly regulating glucose metabolism and insulin sensitivity in vitro and in vivo.
15 November 2002
Original research paper: Nature Medicine 8, 1288 - 1295, (November 2002) |
 | Development: Please release me
Disp proteins are members of the bacterial RND family of transporters, and have now been shown to have a 'new' function in membrane release of Hedgehog.
15 November 2002
Original research paper: Cell 111, 63 - 75, (2002) |
 | Macrophages: Immune evasion by anthrax
Through phosphorylation of an as-yet-unidentified target, p38 synergizes with NF-?B to induce the expression of anti-apoptotic genes in macrophages.
15 November 2002
Original research paper: Science 297, 2048 - 2051, (2002) |
 | Natural killer cells: On guard
A study in Immunity shows that the transcription factor MEF is essential for the expression of perforin by NK cells, providing clues as to the basis of a human genetic disease.
15 November 2002
Original research paper: Immunity 17, 437 - 449, (2002) |
 | Tumorigenesis: Converging paths
In Nature Medicine, Glenn Merlino and colleagues report that defects in several different pathways need to converge to form rhabdomyosarcoma (RMS) tumors, as mice with disruptions in the Cdkn2a locus and activation of the c-Met signaling pathway develop RMS.
15 November 2002
Original research paper: Nature Med. 2, 289 - 300, (7 Oct 2002) |
 | Ion channels: S4 opens another cork
How does the S4 segment of HCN channels behave in response to hyperpolarization? Data from Männikkö et al. indicate that S4 is indeed the voltage sensor of HCN channels, but that, in this case, the inward movement of S4 leads to channel opening.
15 November 2002
Original research paper: Nature 419, 837 - 841, (2002) |
 | Cardiovascular disease: Macrophage LXRs inhibit atherosclerosis
Tangirala et al.show that when LXRs — members of the nuclear hormone receptor superfamily of transcription factors — are expressed by macrophages, they protect against atherosclerosis in mouse models of the disease.
15 November 2002
Original research paper: Proc. Natl Acad. Sci. USA 99, 11896 - 11901, (2002) |
 | Talin the tale of phosphoinositol signaling in cell adhesion
Two independent studies in Nature investigate the role of phosphoinositol signaling at focal adhesions. PtdInsPKI?, the enzyme that generates PtdIns(4,5)P2, interacts with a key component of focal adhesions known as talin. This knowledge gives us fresh insights into the regulatory roles that occur in cell adhesion.
8 November 2002
Original research paper: Nature 420, 85 - 89, (7 November 2002) |
 | DNA replication:
Ku calls time
Donaldson and colleagues, in Genes & Development, show that Ku has a specific function in determining the activation time of telomere-proximal replication origins.
8 November 2002
Original research paper: Genes Dev. 16, 2485 - 2490, (2002) |
 | Oncogenesis: MYC reduces stress
A proteomic analysis has revealed yet another potential function for Myc in tumorigenesis. By reducing adhesion and increasing motility, Myc might promote invasion and metastasis.
8 November 2002
Original research paper: EMBO J. 21, 5088 - 5096, (2002) |
 | Angiogenesis:
Multi-tasking
c-MYC not only has an integral role in promoting cell proliferation and growth but it also acts as a key regulator of angiogenesis.
8 November 2002
Original research paper: Genes Dev. 16, 2530 - 12543, (2002) |
 | Neurophysiology: Cause for excitation
Ingram et al. have found that activation of DAT triggers a current that increases the excitability of midbrain dopamine neurons.
8 November 2002
Original research paper: Nature Neurosci. 5, 971 - 978, (2002) |
 | Development: A new direction for frizzled
Wang et al. now show that the Wnt receptor frizzled 3 is required for the development of major axonal tracts in the mammalian forebrain.
8 November 2002
Original research paper: J. Neurosci. 22, 8563 - 8573, (2002) |
 | Structure-based drug design:
Complex is crystal clear
A new understanding of EGFR activation at the three-dimensional structural level could provide a way to rationally design anti-cancer drugs that block signaling through inhibition of dimerization.
8 November 2002
Original research paper: Cell 110, 763 - 773, (2002) |
 | cAMP regulation of ERK: No role for Rap1
Enserink et al. have used a novel cAMP analogue to demonstrate that the role of Rap1 in cAMP-induced activation of ERK is questionable.
1 November 2002
Original research paper: Nature Cell Biology 4, 901 - 906, (November 2002) |
 | Membrane dynamics:
From cargo to curves
A report by Harvey McMahon and colleagues describes how epsin 1 might act as a crucial link between vesicle formation and the recruitment of cargo.
1 November 2002
Original research paper: Nature 419, 361 - 366, (2002) |
 | Cell signalling: New tricks for DIX
In Nature, Michael Overduin and colleagues reveal that DIX has a role in segregating Dvl into two different intracellular pools, and that by doing so, it controls a critical divergence point in the Wnt signaling pathway.
1 November 2002
Original research paper: Nature 419, 726 - 729, (2002) |
 | HIV: Quality control
Although the frequency of HIV-specific CD8+ T cells is similar in all patients, the T cells of long-term non-progressors limit viral replication by means of their higher proliferative capacity coupled to increased perforin expression.
1 November 2002
Original research paper: Nature Immunol. 98, 1667 - 1677, (7 October 2002) |
 | Drug resistance:
Damage limitation
Benjamin Deverman and colleagues provide evidence that BCL-XL has a functional role in resisting apoptosis when it is caused by cisplatin and other anticancer agents.
1 November 2002
Original research paper: Cell 111, 51 - 62, (2000) |
 | Autoimmune disease:
Lesions with a jagged edge
John et al. show that a signaling pathway that controls oligodendrocyte maturation in the embryo might contribute to the pathogenesis of multiple sclerosis if it is reactivated in the adult.
1 November 2002
Original research paper: Nature Med. 8, 1115 - 1121, (2002) |
