Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity

davidd submitted, created time 10 months 1 week (www.pnas.org)

B-RAF is the most frequent oncogenic protein kinase mutation known. Furthermore, inhibitors targeting "active" protein kinases have demonstrated significant utility in the therapeutic repertoire against cancer. The article represents the entire discovery process of a selective inhibitor , from initial identification through structural and biological studies in animal models to a promising therapeutic for testing in cancer patients bearing B-RafV600E-driven tumors.

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A role for IκB kinase 2 in bipolar spindle assembly

davis submitted, created time 1 year 2 months (www.pnas.org)

IκB kinase 2 (IKK2 or IKKβ) is a component of the IKK complex that coordinates the cellular response to a diverse set of extracellular stimuli, including cytokines, microbial infection, and stress. In response to an external stimulus, the complex is activated, resulting in the phosphorylation and subsequent proteasome-mediated degradation of IκB proteins.

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Mapping phosphoproteins in Mycoplasma genitalium and Mycoplasma pneumoniae

m.giddings submitted, created time 1 year 3 months (www.biomedcentral.com)

Little is known regarding the extent or targets of phosphorylation in mycoplasmas, yet in many other bacterial species phosphorylation is known to play an important role in signaling and regulation of cellular processes. To determine the prevalence of phosphorylation in mycoplasmas, the researchers examined the CHAPS-soluble protein fractions of Mycoplasma genitalium and Mycoplasma pneumoniae by two-dimensional gel electrophoresis (2-DE), using a combination of Pro-Q Diamond phosphoprotein stain and 33P labeling

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MAP kinase phosphatase activity sets the threshold for thymocyte positive selection

doris submitted, created time 1 year 3 months (www.pnas.org)

Phosphorylation of MAP kinases is important for proper translation of T cell antigen receptor (TCR) signals into thymocyte cell fates, but the role of MAP kinase phosphatase (MKP) activity in thymocyte development has not been characterized.

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ATPase activity of KaiC determines the basic timing for circadian clock of cyanobacteria

stephen submitted, created time 1 year 3 months (www.pnas.org)

Self-sustainable oscillation of KaiC phosphorylation has been reconstituted in vitro, demonstrating that this cycle is the basic time generator of the circadian clock of cyanobacteria. Here we show that the ATPase activity of KaiC satisfies the characteristics of the circadian oscillation, the period length, and the temperature compensation.

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Control of Emi2 activity and stability through Mos-mediated recruitment of PP2A

franklin submitted, created time 1 year 3 months (www.pnas.org)

Before fertilization, vertebrate eggs are arrested in meiosis II by cytostatic factor (CSF), which holds the anaphase-promoting complex (APC) in an inactive state. It was recently reported that Mos, an integral component of CSF, acts in part by promoting the Rsk-mediated phosphorylation of the APC inhibitor Emi2/Erp1.

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Functions of OsBZR1 and 14-3-3 proteins in brassinosteroid signaling in rice

jiangyun submitted, created time 1 year 4 months (www.pnas.org)

Brassinosteroids (BR) are essential growth hormones found throughout the plant kingdom. BR bind to the receptor kinase BRI1 on the cell surface to activate a signal transduction pathway that regulates nuclear gene expression and plant growth. To understand the downstream BR signaling mechanism in rice, we studied the function of OsBZR1 using reverse genetic approaches and identified OsBZR1-interacting proteins

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Speeding 'fingertip' discovery -- 20 years of protein info in 1 place

athena submitted, created time 1 year 8 months (www.biologynews.net)

"Researchers at Johns Hopkins took advantage of a new technique that reads the makeup of proteins to identify nearly all chemical changes nature makes by adding phosphate to proteins manufactured in human cells. ”

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PRAS40 Is an Insulin-Regulated Inhibitor of the mTORC1 Protein Kinase

alpha submitted, created time 1 year 9 months (www.molecule.org)

"The heterotrimeric mTORC1 protein kinase nucleates a signaling network that promotes cell growth in response to insulin and becomes constitutively active in cells missing the TSC1 or TSC2 tumor suppressors."

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Biphasic Coupling of Neuronal Nitric Oxide Synthase Phosphorylation to the NMDA Receptor Regulates AMPA Receptor Trafficking and Neuronal Cell Death

julie submitted, created time 1 year 9 months (www.jneurosci.org)

”Postsynaptic nitric oxide (NO) production affects synaptic plasticity and neuronal cell death. Ca2+ fluxes through the NMDA receptor (NMDAR) stimulate the production of NO by neuronal nitric oxide synthase (nNOS).“

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Netrin signaling leading to directed growth cone steering

amanda submitted, created time 1 year 9 months (www.sciencedirect.com)

"In the developing nervous system, nerve cells and axons respond to various attractive and repulsive guidance cues while traveling to their final destination. Netrins are bifunctional guidance cues that attract several classes of axons but repel others. The response of an axon to netrins is dictated by the composition of netrin receptors on the cell surface and the internal state of the growth cone. Recent analyses have identified several signal transduction pathways that contribute to netrin-mediated guidance

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Evolution of Ime2 Phosphorylation Sites on Cdk1 Substrates Provides a Mechanism to Limit the Effects of the Phosphatase Cdc14 in Meiosis

julie submitted, created time 1 year 9 months (www.molecule.org)

"Progression through meiosis in yeast is governed by the cyclin-dependent kinase Cdk1, in concert with a related kinase called Ime2. It remains unclear how these kinases collaborate to meet the unique demands of meiotic progression. "

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“MDM2-Regulated Degradation of HIPK2 Prevents p53Ser46 Phosphorylation and DNA Damage-Induced Apoptosis”

diggman submitted, created time 1 year 9 months (www.sciencedirect.com)

"In response to DNA damage, p53 induces either cell-cycle arrest or apoptosis by differential transcription of several target genes and through transcription-independent apoptotic functions. p53 phosphorylation at Ser46 by HIPK2 is one determinant of the outcome because it takes place only upon severe, nonrepairable DNA damage that irreversibly drives cells to apoptosis. p53 represses its proapoptotic activator HIPK2 via MDM2-mediated degradation, whereas a degradation-resistant HIPK2 mutant has increased apoptotic activity

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A Network Analysis of Changes in Molecular Interactions in Cellular Signaling

BIOBOSS submitted, created time 1 year 9 months (www.mcponline.org)

Multiprotein complexes play an essential role in the propagation and integration of cellular signals. We show that complex formation through phosphorylation of the scaffolding protein LAT (linker for activation of T-cells) acted as a signal amplifier. PLC 1 deficiency increased the resting state levels of LAT-dependent complexes and augmented the recruitment of the phosphatase SHPTP2 into complexes.

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Phosphorylation of B14.5a Subunit from Bovine Heart Complex I Identified by Titanium Dioxide Selective Enrichment and Shotgun Proteomics

captainclaw submitted, created time 1 year 10 months (www.mcponline.org)

“Shotgun proteomics was used to study the steady phosphorylation state of NADH:ubiquinone oxidoreductase (complex I) subunits from bovine heart mitochondria. A total tryptic digestion of enzymatically active complex I was performed, and the resulting peptide mixture was subjected to phosphopeptide enrichment by the use of titanium dioxide (TiO2). The phosphopeptide-enriched fraction was separated and analyzed with nanoscale reverse-phase HPLC-ESI-MS/MS in single information-dependent acquisition. ”

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