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Cell type-specific transcription during Bacillus sporulation is established by σ F . SpoIIAB is an anti-σ that binds and negatively regulates σ F , as well as a serine kinase that phosphorylates and inactivates the anti-anti-σ SpoIIAA. The crystal structure of σ F bound to the SpoIIAB dimer in the low-affinity, ADP form has been determined at 2.9 Å resolution. SpoIIAB adopts...
Rac, a member of the Rho family of monomeric GTPases, is an integrator of intracellular signaling in a wide range of cellular processes. We have purified a PtdIns(3,4,5)P 3 -sensitive activator of Rac from neutrophil cytosol. It is an abundant, 185 kDa guanine-nucleotide exchange factor (GEF), which we cloned and named P-Rex1. The recombinant enzyme has Rac-GEF activity that is directly, substantially,...
We show that a vascular endothelial growth factor (VEGF) pathway controls embryonic migrations of blood cells (hemocytes) in Drosophila. The VEGF receptor homolog is expressed in hemocytes, and three VEGF homologs are expressed along hemocyte migration routes. A receptor mutation arrests progression of blood cell movement. Mutations in Vegf17E or Vegf27Cb have no effect, but simultaneous inactivation...
Cytokinesis is the physical act of separating daughter cells, allowing them to become separate entities. Recent studies have revealed that membrane insertion for furrowing and scission of the residual bridge is a key aspect of animal cytokinesis.
The striking behavioral phenotypes of mice lacking the TRP2 ion channel have highlighted the importance of the vomeronasal organ in gender-specific sexual behavior.
Mutations in the Artemis protein in humans result in hypersensitivity to DNA double-strand break-inducing agents and absence of B and T lymphocytes (radiosensitive severe combined immune deficiency [RS-SCID]). Here, we report that Artemis forms a complex with the 469 kDa DNA-dependent protein kinase (DNA-PK cs ) in the absence of DNA. The purified Artemis protein alone possesses single-strand-specific...
Wnt regulation of β-catenin degradation is essential for development and carcinogenesis. β-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation, which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC). Here we describe another Axin-associated kinase, whose phosphorylation...
Recent structural studies on calmodulin complexes with anthrax adenylyl cyclase and rat Ca 2+ -activated K + channel have uncovered unexpected ways by which calmodulin interacts with target proteins.
In Arabidopsis, RPM1 confers resistance against Pseudomonas syringae expressing either of two sequence unrelated type III effectors, AvrRpm1 or AvrB. An RPM1-interacting protein (RIN4) coimmunoprecipitates from plant cell extracts with AvrB, AvrRpm1, or RPM1. Reduction of RIN4 protein levels inhibits both the hypersensitive response and the restriction of pathogen growth controlled by RPM1. RIN4 reduction...
Complement receptor type 1 (CR1 or CD35) is a multiple modular protein that mediates the immune adherence phenomenon, a fundamental event for destroying microbes and initiating an immunological response. It fulfills this role through binding C3b/C4b-opsonized foreign antigens. The structure of the principal C3b/C4b binding site (residues 901-1095) of CR1 is reported, revealing three complement control...
In this issue of Cell, a study by N. Cho and coworkers provides insight into the role of vascular endothelial growth factor (VEGF) signaling in Drosophila hematopoiesis (Cho et al., 2002). Their work suggests that an ancestral function of VEGF was to guide blood cell migration and highlights the conservation of at least one aspect of VEGF signaling during evolution.
T lymphocyte selection and lineage commitment in the thymus requires multiple signals. Herein, CD4 + T cell generation required engagement of CD83, a surface molecule expressed by thymic epithelial and dendritic cells. CD83-deficient (CD83 -/- ) mice had a specific block in CD4 + single-positive thymocyte development without increased CD4 + CD8 + double-...
The secreted signaling molecule Hedgehog regulates gene expression in target cells in part by preventing proteolysis of the full-length Cubitus interruptus (Ci-155) transcriptional activator to the Ci-75 repressor form. Ci-155 proteolysis depends on phosphorylation at three sites by Protein Kinase A (PKA). We show that these phosphoserines prime further phosphorylation at adjacent Glycogen Synthase...
Dynamic regulation of AMPA-type glutamate receptors represents a primary mechanism for controlling synaptic strength, though mechanisms for this process are poorly understood. The palmitoylated postsynaptic density protein, PSD-95, regulates synaptic plasticity and associates with the AMPA receptor trafficking protein, stargazin. Here, we identify palmitate cycling on PSD-95 at the synapse and find...
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