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.
 | Cancer: Trk'd into moving
The neurotrophic receptor tyrosine kinase TrkB has been identified as a potent and specific suppressor of caspase-associated anoikis, and has been linked with the promotion of metastasis.
Original research paper: Nature 430, 1034 – 1039, (26 August 2004) |
 | Apoptosis: Upstream, downstream
Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain.
Original research paper: Cell 117, 773 – 786, (2004) |
 | In brief: August 2004
Cytoskeleton | Cytoskeleton | Mechanism of disease | Signalling | Immune evasion | Cytokines | Reproductive immunology | Transplantation | Breast Cancer | Gene Expression | Plant Genetics | Neurogenetics | Development |
 | Cytoskeleton: A signal to collapse
Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through a2ß1 integrin.
Original research paper: J. Cell Biol. 166, 97 – 109, (2004) |
 | Lipid metabolism: Sensing change
Researchers report new insights into how cells coordinate changes in the composition of their cellular membranes with lipid metabolism.
Original research paper: Science 304, 1644 – 1647, (2004) |
 | T-cell development: Mi-2ß acting positively
The chromatin remodeler Mi–2ß is required for CD4 expression and T cell development.
Original research paper: Immunity 20, 719 – 733, (2004) |
 | Metastasis: Stick or twist?
TWIST — a master gene that controls epithelial-mesenchymal transition in embryogenesis mdash; is required for metastasis in epithelial-derived breast tumors.
Original research paper: Cell 117, 927 – 939, (2004) |
 | Angiogenesis: Recruitment drive
VEGF–null cells require PDGFRa signaling-mediated stromal fibroblast recruitment for tumorigenesis.
Original research paper: EMBO J. 23, 2800 – 2810, (2004) |
 | Tumour viruses: A genetic switch
Two groups have used gene–expression profiling to show that Kaposi's–sarcoma–associated herpesvirus activates expression of lymphatic–specific genes, including VEGFR3.
Original research paper: Nature Genet. 36, 683 – 685, (2004) |
 | Cancer genetics: A guardian and a suppressor
MUS81 endonuclease is required in mammals for genomic stability and tumor suppression.
Original research paper: Science 304, 1822 – 1826, (2004) |
 | Synaptic physiology: A scaffolder at the active zone
The active zone protein RIM1a has multiple roles in late stages of neurotransmitter release.
Original research paper: Neuron 42, 889 – 896, (2004) |
 | Ion channels: TRPing out on translocation
Growth factor stimulation initiates a response termed 'rapid vesicular insertion of TRP' (RiVIT), whereby canonical transient receptor potential (TRPC) ion channels are rapidly translocated to the cell surface from vesicles held in reserve just under the plasma membrane.
Original research paper: Nature Cell Biology 6, 709 – 720, (2004) |
 | Cytoskeleton: Turn it on
Phosphorylation of RhoGDI by PAK1 mediates dissociation of Rac GTPase.
Original research paper: Mol. Cell 15, 117 – 127, (2004) |
 | Lymphocyte responses: NFAT5: Helping out in stressful times
Lymphocytes are exposed to hypertonic environments in lymphoid organs and depend on an osmotic–stress response mediated through the transcription factor NFAT5 for their survival and function.
Original research paper: Proc. Natl Acad. Sci. USA 101, 10673 – 10678, (2004) |
 | Innate immunity: Selective activation
Regulation of Toll/IL–1–receptor–mediated gene expression by the inducible nuclear protein I?B?.
Original research paper: Nature 430, 218 – 222, (2004) |
 | Tumour supressor: Benign association
The LKB1 tumor suppressor negatively regulates mTOR signaling.
Original research paper: Cancer Cell 18, 1533 – 1538, (20 July 2004) |
 | Neuronal plasticity: PARP1 allows lasting memories
Long–term memory requires polyADP–ribosylation.
Original research paper: Science 304, 1820 – 1822, (2004) |
 | Anticancer drugs: Taking out the chaperone
Hsp90 inhibitors have multiple antitumor–specific effects, meaning that they might be active in a broad range of cancers.
Original research paper: Chem. Biol. 11, 787 – 797, (2004) |
 | Cancer: MAD about genomic instability
Retinoblastoma (Rb) inactivation promotes genomic instability in cancerous cells by uncoupling cell cycle progression from mitotic control.
Original research paper: Nature 430, 797 – 802, (12 August 2004) |
 | Gene regulation: On target
SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells.
Original research paper: Nature Cell Biol. 6, 731 – 740, (2004) |
 | Membrane trafficking: Actin' at a new site
Actin and the HIP1R linker protein have roles in the budding from the trans-Golgi network of clathrin-coated vesicles that are bound for lysosomes.
Original research paper: J. Cell Biol. 165, 781 – 788, (2004) |
 | Inflammation: A useful CARD to hold
NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses.
Original research paper: Nature Immunol. 5, 800 – 808, (2004) |
 | B cells: MITF's calming influence
Active inhibition of plasma cell development in resting B cells by microphthalmia-associated transcription factor.
Original research paper: J. Exp. Med. 200, 115 – 122, (2004) |
 | Immunology: Receptors and effectors
The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy.
Original research paper: J. Exp. Med. 199, 1659 – 1669, (2004) |
 | Chemical tools: A substrate finds its kinase
Instead of going down the well-beaten path of taking a kinase and looking for its substrate, a chemical cross-linker has been devised that allows the substrate to find its kinase.
Original research paper: J. Am. Chem. Soc. 126, 9160 – 9161, (2004) |
 | Inflammation: Protein A causes invasion of the PMNs
Bacterial protein A of Staphylococcus aureus can initiate TNF-a signaling responses in lung epithelia by binding to TNFR1, leading to inflammatory responses and pneumonia.
Original research paper: Nature Medicine 10, 842 – 848, (2004) |
 | Tumour suppressors: Pinning down p73
Two papers shed new light on the molecular mechanisms that regulate the function and stability of p73 – a close relative of the tumor suppressor p53.
Original research paper: Mol. Cell 14, 625 – 636, (2004) |
 | T-cell signalling: Getting faster with experience
Differences in signaling molecule organization between naive and memory CD4+ T lymphocytes.
Original research paper: J. Immunol. 173, 33 – 41, (2004) |
 | Oncogenes: Two of a kind
Two cytoskeletal proteins, p21-activated kinase 1 and the dynein light chain 1, interact to promote the survival and tumorigenic potential of breast cancer cells.
Original research paper: Cancer Cell 5, 575 – 585, (2004) |
 | Axon guidance: Knowing when to stop
Retinal axon response to ephrin–As shows a graded, concentration–dependent transition from growth promotion to inhibition.
Original research paper: Neuron 42, 717 – 730, (2004) |
 | Autoimmune diabetes: NKG2D receptor: a therapeutic target?
NKG2D blockade prevents autoimmune diabetes in NOD mice.
Original research paper: Immunity 20, 757 – 767, (2004) |
