Search Results - "WILLIAMS, Roger L"

VPS34 complexes from a structural perspective by Ohashi, Yohei, Tremel, Shirley, Williams, Roger L.

“…VPS34 phosphorylates phosphatidylinositol to produce PtdIns3P and is the progenitor of the phosphoinositide 3-kinase (PI3K) family. VPS34 has a simpler domain…”
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Activation of GCN2 by the ribosomal P-stalk by Inglis, Alison J., Masson, Glenn R., Shao, Sichen, Perisic, Olga, McLaughlin, Stephen H., Hegde, Ramanujan S., Williams, Roger L.

“…Cells dynamically adjust their protein translation profile to maintain homeostasis in changing environments. During nutrient stress, the kinase general control…”
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Structure and flexibility of the endosomal Vps34 complex reveals the basis of its function on membranes by Rostislavleva, Ksenia, Soler, Nicolas, Ohashi, Yohei, Zhang, Lufei, Pardon, Els, Burke, John E., Masson, Glenn R., Johnson, Chris, Steyaert, Jan, Ktistakis, Nicholas T., Williams, Roger L.

“…Phosphatidylinositol 3-kinase Vps34 complexes regulate intracellular membrane trafficking in endocytic sorting, cytokinesis, and autophagy. We present the 4.4…”
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Oncogenic mutations mimic and enhance dynamic events in the natural activation of phosphoinositide 3-kinase p110α (PIK3CA) by Burke, John E, Perisic, Olga, Masson, Glenn R, Vadas, Oscar, Williams, Roger L

“…The p110α catalytic subunit (PIK3CA) is one of the most frequently mutated genes in cancer. We have examined the activation of the wild-type p110α/p85α and a…”
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The ribosomal P-stalk couples amino acid starvation to GCN2 activation in mammalian cells by Harding, Heather P, Ordonez, Adriana, Allen, Felicity, Parts, Leopold, Inglis, Alison J, Williams, Roger L, Ron, David

“…The eukaryotic translation initiation factor 2α (eIF2α) kinase GCN2 is activated by amino acid starvation to elicit a rectifying physiological program known as…”
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Tor forms a dimer through an N-terminal helical solenoid with a complex topology by Baretić, Domagoj, Berndt, Alex, Ohashi, Yohei, Johnson, Christopher M., Williams, Roger L.

“…The target of rapamycin (Tor) is a Ser/Thr protein kinase that regulates a range of anabolic and catabolic processes. Tor is present in two complexes, TORC1…”
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Structure of Lipid Kinase p110β/p85β Elucidates an Unusual SH2-Domain-Mediated Inhibitory Mechanism by Zhang, Xuxiao, Vadas, Oscar, Perisic, Olga, Anderson, Karen E., Clark, Jonathan, Hawkins, Phillip T., Stephens, Len R., Williams, Roger L.

“…Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. The structure of a p110β/p85β complex identifies an inhibitory…”
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5‑(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)­pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology by Beaufils, Florent, Cmiljanovic, Natasa, Cmiljanovic, Vladimir, Bohnacker, Thomas, Melone, Anna, Marone, Romina, Jackson, Eileen, Zhang, Xuxiao, Sele, Alexander, Borsari, Chiara, Mestan, Jürgen, Hebeisen, Paul, Hillmann, Petra, Giese, Bernd, Zvelebil, Marketa, Fabbro, Doriano, Williams, Roger L, Rageot, Denise, Wymann, Matthias P

“…Phosphoinositide 3-kinase (PI3K) is deregulated in a wide variety of human tumors and triggers activation of protein kinase B (PKB/Akt) and mammalian target of…”
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Structural basis for activation and inhibition of class I phosphoinositide 3-kinases by Vadas, Oscar, Burke, John E, Zhang, Xuxiao, Berndt, Alex, Williams, Roger L

“…Phosphoinositide 3-kinases (PI3Ks) are implicated in a broad spectrum of cellular activities, such as growth, proliferation, differentiation, migration, and…”
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A Role for the ESCRT System in Cell Division in Archaea by Samson, Rachel Y., Obita, Takayuki, Freund, Stefan M., Williams, Roger L., Bell, Stephen D.

“…Archaea are prokaryotic organisms that lack endomembrane structures. However, a number of hyperthermophilic members of the Kingdom Crenarchaea, including…”
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The intrinsically disordered tails of PTEN and PTEN-L have distinct roles in regulating substrate specificity and membrane activity by Masson, Glenn R, Perisic, Olga, Burke, John E, Williams, Roger L

“…Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a lipid and protein phosphatase, and both activities are necessary for its role as a tumour…”
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Regulation of PI3K by PKC and MARCKS: Single-Molecule Analysis of a Reconstituted Signaling Pathway by Ziemba, Brian P., Burke, John E., Masson, Glenn, Williams, Roger L., Falke, Joseph J.

“…In chemotaxing ameboid cells, a complex leading-edge signaling circuit forms on the cytoplasmic leaflet of the plasma membrane and directs both actin and…”
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Structural basis for VPS34 kinase activation by Rab1 and Rab5 on membranes by Tremel, Shirley, Ohashi, Yohei, Morado, Dustin R., Bertram, Jessie, Perisic, Olga, Brandt, Laura T. L., von Wrisberg, Marie-Kristin, Chen, Zhuo A., Maslen, Sarah L., Kovtun, Oleksiy, Skehel, Mark, Rappsilber, Juri, Lang, Kathrin, Munro, Sean, Briggs, John A. G., Williams, Roger L.

“…The lipid phosphatidylinositol-3-phosphate (PI3P) is a regulator of two fundamental but distinct cellular processes, endocytosis and autophagy, so its…”
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Deconvolution of Buparlisib’s mechanism of action defines specific PI3K and tubulin inhibitors for therapeutic intervention by Bohnacker, Thomas, Prota, Andrea E., Beaufils, Florent, Burke, John E., Melone, Anna, Inglis, Alison J., Rageot, Denise, Sele, Alexander M., Cmiljanovic, Vladimir, Cmiljanovic, Natasa, Bargsten, Katja, Aher, Amol, Akhmanova, Anna, Díaz, J. Fernando, Fabbro, Doriano, Zvelebil, Marketa, Williams, Roger L., Steinmetz, Michel O., Wymann, Matthias P.

“…BKM120 (Buparlisib) is one of the most advanced phosphoinositide 3-kinase (PI3K) inhibitors for the treatment of cancer, but it interferes as an off-target…”
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Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases by Shokat, Kevan M, Apsel, Beth, Blair, Jimmy A, Gonzalez, Beatriz, Nazif, Tamim M, Feldman, Morri E, Aizenstein, Brian, Hoffman, Randy, Williams, Roger L, Knight, Zachary A

“…The clinical success of multitargeted kinase inhibitors has stimulated efforts to identify promiscuous drugs with optimal selectivity profiles. It remains…”
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Dynamics of the Phosphoinositide 3-Kinase p110δ Interaction with p85α and Membranes Reveals Aspects of Regulation Distinct from p110α by Burke, John E., Vadas, Oscar, Berndt, Alex, Finegan, Tara, Perisic, Olga, Williams, Roger L.

“…Phosphoinositide 3-kinase δ is upregulated in lymphocytic leukemias. Because the p85-regulatory subunit binds to any class IA subunit, it was assumed there is…”
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Mechanism of Two Classes of Cancer Mutations in the Phosphoinositide 3-Kinase Catalytic Subunit by Miled, Nabil, Yan, Ying, Hon, Wai-Ching, Perisic, Olga, Zvelebil, Marketa, Inbar, Yuval, Schneidman-Duhovny, Dina, Wolfson, Haim J., Backer, Jonathan M., Williams, Roger L.

“…Many human cancers involve up-regulation of the phosphoinositide 3-kinase PI3Kα, with oncogenic mutations identified in both the p110α catalytic and the p85α…”
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Human PI3Kγ deficiency and its microbiota-dependent mouse model reveal immunodeficiency and tissue immunopathology by Takeda, Andrew J., Maher, Timothy J., Zhang, Yu, Lanahan, Stephen M., Bucklin, Molly L., Compton, Susan R., Tyler, Paul M., Comrie, William A., Matsuda, Makoto, Olivier, Kenneth N., Pittaluga, Stefania, McElwee, Joshua J., Long Priel, Debra A., Kuhns, Douglas B., Williams, Roger L., Mustillo, Peter J., Wymann, Matthias P., Koneti Rao, V., Lucas, Carrie L.

“…Phosphatidylinositol 3-kinase-gamma (PI3Kγ) is highly expressed in leukocytes and is an attractive drug target for immune modulation. Different experimental…”
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Membrane characteristics tune activities of endosomal and autophagic human VPS34 complexes by Ohashi, Yohei, Tremel, Shirley, Masson, Glenn Robert, McGinney, Lauren, Boulanger, Jerome, Rostislavleva, Ksenia, Johnson, Christopher M, Niewczas, Izabella, Clark, Jonathan, Williams, Roger L

“…The lipid kinase VPS34 orchestrates diverse processes, including autophagy, endocytic sorting, phagocytosis, anabolic responses and cell division. VPS34 forms…”
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Structural Insights into Arl1-Mediated Targeting of the Arf-GEF BIG1 to the trans-Golgi by Galindo, Antonio, Soler, Nicolas, McLaughlin, Stephen H., Yu, Minmin, Williams, Roger L., Munro, Sean

“…The GTPase Arf1 is the major regulator of vesicle traffic at both the cis- and trans-Golgi. Arf1 is activated at the cis-Golgi by the guanine nucleotide…”
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