25-01-2011 | Arif, Abul; Jia, Jie; Moodt, Robyn A.; DiCorleto, Paul E.; Fox, Paul L., Proceedings of the National Academy of Sciences current issue, 2011

Cyclin-dependent kinase 5 (Cdk5) is an atypical but essential member of the Cdk kinase family, and its dysregulation or deletion has been implicated in inflammation-related disorders by an undefined mechanism. Here we show that Cdk5 is an indispensable activator of the GAIT (IFN-γ–activated ...

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25-01-2011 | Maag, David; Maxwell, Micah J.; Hardesty, Douglas A.; Boucher, Katie L.; Choudhari, Namrata; Hanno, Adam G.; Ma, Jen ..., Proceedings of the National Academy of Sciences current issue, 2011

The second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3), formed by the p110 family of PI3-kinases, promotes cellular growth, proliferation, and survival, in large part by activating the protein kinase Akt/PKB. We show that inositol polyphosphate multikinase (IPMK) ...

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25-01-2011 | Shi, Rong; McDonald, Laura; Cui, Qizhi; Matte, Allan; Cygler, Miroslaw; Ekiel, Irena, Proceedings of the National Academy of Sciences current issue, 2011

The Escherichia coli dihydroxyacetone (Dha) kinase is an unusual kinase because (i) it uses the phosphoenolpyruvate carbohydrate: phosphotransferase system (PTS) as the source of high-energy phosphate, (ii) the active site is formed by two subunits, and (iii) the substrate is covalently bound ...

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18-01-2011 | Blasi, Giuseppe; Napolitano, Francesco; Ursini, Gianluca; Taurisano, Paolo; Romano, Raffaella; Caforio, Grazia; Fazi ..., Proceedings of the National Academy of Sciences current issue, 2011

The D2/AKT1/GSK-3β signaling pathway has been involved in the downstream intracellular effects of dopamine, in the pathophysiology of cognitive deficits and related brain activity in schizophrenia, as well as in response to treatment with antipsychotics. Polymorphisms in the D2 (DRD2 ...

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18-01-2011 | Chen, Y. Erin; Tropini, Carolina; Jonas, Kristina; Tsokos, Christos G.; Huang, Kerwyn C.; Laub, Michael T., Proceedings of the National Academy of Sciences current issue, 2011

Spatial asymmetry is crucial to development. One mechanism for generating asymmetry involves the localized synthesis of a key regulatory protein that diffuses away from its source, forming a spatial gradient. Although gradients are prevalent in eukaryotes, at both the tissue and intracellular ...

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11-01-2011 | Ding, Yunmin; Won, Lisa; Britt, Jonathan P.; Lim, Sean Austin O.; McGehee, Daniel S.; Kang, Un Jung, Proceedings of the National Academy of Sciences current issue, 2011

Treatment of Parkinson disease (PD) with l-3,4-dihydroxyphenylalanine (l-DOPA) dramatically relieves associated motor deficits, but l-DOPA–induced dyskinesias (LID) limit the therapeutic benefit over time. Previous investigations have noted changes in striatal medium spiny neurons, including ...

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11-01-2011 | Kim, Myungjin; McGinnis, William, Proceedings of the National Academy of Sciences current issue, 2011

Grainy head (GRH) is a key transcription factor responsible for epidermal barrier formation and repair, whose function is highly conserved across diverse animal species. However, it is not known how GRH function is reactivated to repair differentiated epidermal barriers after wounding. Here, ...

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11-01-2011 | Beharry, Zanna; Mahajan, Sandeep; Zemskova, Marina; Lin, Ying-Wei; Tholanikunnel, Baby G.; Xia, Zuping; Smith, Charl ..., Proceedings of the National Academy of Sciences current issue, 2011

The serine/threonine Pim kinases are overexpressed in solid cancers and hematologic malignancies and promote cell growth and survival. Here, we find that a novel Pim kinase inhibitor, SMI-4a, or Pim-1 siRNA blocked the rapamycin-sensitive mammalian target of rapamycin (mTORC1) activity by ...

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04-01-2011 | Chao, Suzan K.; Lin, Juan; Brouwer-Visser, Jurriaan; Smith, Amos B.; Horwitz, Susan Band; McDaid, Hayley M., Proceedings of the National Academy of Sciences current issue, 2011

Discodermolide is a microtubule-stabilizing agent that induces accelerated cell senescence. A discodermolide-resistant cell line, AD32, was generated from the human lung cancer cell line A549. We hypothesize that the major resistance mechanism in these cells is escape from accelerated ...

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04-01-2011 | Tyagarajan, Shiva K.; Ghosh, Himanish; Yévenes, Gonzalo E.; Nikonenko, Irina; Ebeling, Claire; Schwerdel, Cornelia; ..., Proceedings of the National Academy of Sciences current issue, 2011

Postsynaptic scaffolding proteins ensure efficient neurotransmission by anchoring receptors and signaling molecules in synapse-specific subcellular domains. In turn, posttranslational modifications of scaffolding proteins contribute to synaptic plasticity by remodeling the postsynaptic ...

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