Swanton, Charles, Szallasi, Zoltan, Brenton, James D, Downward, Julian
Abstract The widespread introduction of high throughput RNA interference screening technology has revealed tumour drug sensitivity pathways to common cytotoxics such as paclitaxel, doxorubicin and...
The mitochondrial protese HtrA2 is regulated by Parkinson's disease-associated kinase PINK1 (2007)
Plun-Favreau, Helene, Klupsch, Kristina., Gandhi, Sonia, Kjaer, Svend, Frith, David, Harvey, Kirsten, ...
This is the authors' final draft of the version published as Nature Cell Biology, 2007, 9 (11), pp.1243-52. The final published version is available online at...
Véronique Calleja, Damien Alcor, Michel Laguerre, Jongsun Park, Borivoj Vojnovic, Brian A. Hemmings, ...
Protein kinase B (PKB/Akt) is a pivotal regulator of diverse metabolic, phenotypic, and antiapoptotic cellular controls and has been shown to be a key player in cancer progression. Here, using...
Minimizing the risk of reporting false positives in large-scale RNAi screens (2006)
Echeverri, Christophe J, Beachy, Philip A, Baum, Buzz, Boutros, Michael, Buchholz, Frank, Chanda, Sumit K, ...
Large-scale RNA interference (RNAi)-based analyses, very much as other 'omic' approaches, have inherent rates of false positives and negatives. The variability in the standards of care applied to...
p110δ, a novel phosphoinositide 3-kinase in leukocytes
Vanhaesebroeck, Bart, Welham, Melanie J., Kotani, Kei, Stein, Rob, Warne, Patricia H., Zvelebil, Markéta J., ...
Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that have been implicated in signal transduction through tyrosine kinase- and heterotrimeric G-protein-linked receptors. We report...
Sethi, Tariq, Ginsberg, Mark H., Downward, Julian, Hughes, Paul E.
The rapid modulation of ligand-binding affinity (“activation”) is a central property of the integrin family of cell adhesion receptors. The small GTP-binding protein Ras and its downstream...
Wennström, Stefan, Downward, Julian
The paradigm for activation of Ras and extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP) kinase by extracellular stimuli via tyrosine kinases, Shc, Grb2, and Sos does not...
De Rooij, Johan, Marte, Barbara, Downward, Julian, Bos, Johannes L., Burgering, Boudewijn M. T.
Regulation of phosphoinositide 3-kinase (PI 3-kinase) can occur by binding of the regulatory p85 subunit to tyrosine-phosphorylated proteins and by binding of the p110 catalytic subunit to activated...
Marani, Michela, Tenev, Tencho, Hancock, David, Downward, Julian, Lemoine, Nicholas R.
Bim (Bcl-2-interacting mediator of cell death) is a member of the BH3 domain-only subgroup of Bcl-2 family members, for which three splice variants have been described. Bim is expressed in many...
Pardo, Olivier E., Lesay, Adeline, Arcaro, Alexandre, Lopes, Rita, Ng, Bee Ling, Warne, Patricia H., ...
The mitochondrial release of cytochrome c and Smac/DIABLO has been implicated in the activation of apoptosis in response to cell stress. Smac promotes cytochrome c-induced activation of caspases by...
Lehmann, Kerstin, Janda, Elzbieta, Pierreux, Christophe E., Rytömaa, Marjatta, Schulze, Almut, McMahon, Martin, ...
c-Raf-1 is a major effector of Ras proteins, responsible for activation of the ERK MAP kinase pathway and a critical regulator of both normal growth and oncogenic transformation. Using an inducible...
Pardo, Olivier E., Lesay, Adeline, Arcaro, Alexandre, Lopes, Rita, Ng, Bee Ling, Warne, Patricia H., ...
Schulze, Almut, Nicke, Barbara, Warne, Patricia H., Tomlinson, Simon, Downward, Julian
The Raf protein kinases are major effectors of Ras GTPases and key components of the transcriptional response to serum factors, acting at least in part through the extracellular signal-regulated...
Martins, L. Miguel, Morrison, Alastair, Klupsch, Kristina, Fedele, Valentina, Moisoi, Nicoleta, Teismann, Peter, ...
The serine protease HtrA2/Omi is released from the mitochondrial intermembrane space following apoptotic stimuli. Once in the cytosol, HtrA2/Omi has been implicated in promoting cell death by binding...
Monitoring conformational changes of proteins in cells by fluorescence lifetime imaging microscopy.
Calleja, Véronique, Ameer-Beg, Simon M, Vojnovic, Borivoj, Woscholski, Rudiger, Downward, Julian, Larijani, Banafshé
To be able to detect in situ changes in protein conformation without perturbing the physiological environment would be a major step forward in understanding the precise mechanism occurring in protein...
Ras protein regulation by G-protein-coupled receptors has been thought to occur through transactivation of receptor tyrosine kinases. New evidence suggests that these two receptor types independently...
Analysis of the transcriptional program induced by Raf in epithelial cells
Schulze, Almut, Lehmann, Kerstin, Jefferies, Harold B.J., McMahon, Martin, Downward, Julian
Activation of the Raf/MAP kinase pathway is a critical event in tumorigenesis induced by RAS and other oncogenes, a major role of this signaling system being the regulation of cellular transcription...
Katso, Roy M., Pardo, Olivier E., Palamidessi, Andrea, Franz, Clemens M., Marinov, Marin, De Laurentiis, Angela, ...
Receptor-linked class I phosphoinositide 3-kinases (PI3Ks) induce assembly of signal transduction complexes through protein–protein and protein–lipid interactions that mediate cell proliferation,...
p110δ, a novel phosphoinositide 3-kinase in leukocytes
Vanhaesebroeck, Bart, Welham, Melanie J., Kotani, Kei, Stein, Rob, Warne, Patricia H., Zvelebil, Markéta J., ...
Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that have been implicated in signal transduction through tyrosine kinase- and heterotrimeric G-protein-linked receptors. We report...
Sethi, Tariq, Ginsberg, Mark H., Downward, Julian, Hughes, Paul E.
The rapid modulation of ligand-binding affinity (“activation”) is a central property of the integrin family of cell adhesion receptors. The small GTP-binding protein Ras and its downstream...
Wennström, Stefan, Downward, Julian
The paradigm for activation of Ras and extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP) kinase by extracellular stimuli via tyrosine kinases, Shc, Grb2, and Sos does not...
De Rooij, Johan, Marte, Barbara, Downward, Julian, Bos, Johannes L., Burgering, Boudewijn M. T.
Regulation of phosphoinositide 3-kinase (PI 3-kinase) can occur by binding of the regulatory p85 subunit to tyrosine-phosphorylated proteins and by binding of the p110 catalytic subunit to activated...
Marani, Michela, Tenev, Tencho, Hancock, David, Downward, Julian, Lemoine, Nicholas R.
Bim (Bcl-2-interacting mediator of cell death) is a member of the BH3 domain-only subgroup of Bcl-2 family members, for which three splice variants have been described. Bim is expressed in many...
Pardo, Olivier E., Lesay, Adeline, Arcaro, Alexandre, Lopes, Rita, Ng, Bee Ling, Warne, Patricia H., ...
The mitochondrial release of cytochrome c and Smac/DIABLO has been implicated in the activation of apoptosis in response to cell stress. Smac promotes cytochrome c-induced activation of caspases by...
Analysis of the transcriptional program induced by Raf in epithelial cells
Schulze, Almut, Lehmann, Kerstin, Jefferies, Harold B.J., McMahon, Martin, Downward, Julian
Activation of the Raf/MAP kinase pathway is a critical event in tumorigenesis induced by RAS and other oncogenes, a major role of this signaling system being the regulation of cellular transcription...
Lehmann, Kerstin, Janda, Elzbieta, Pierreux, Christophe E., Rytömaa, Marjatta, Schulze, Almut, McMahon, Martin, ...
c-Raf-1 is a major effector of Ras proteins, responsible for activation of the ERK MAP kinase pathway and a critical regulator of both normal growth and oncogenic transformation. Using an inducible...
Pardo, Olivier E., Lesay, Adeline, Arcaro, Alexandre, Lopes, Rita, Ng, Bee Ling, Warne, Patricia H., ...
Schulze, Almut, Nicke, Barbara, Warne, Patricia H., Tomlinson, Simon, Downward, Julian
The Raf protein kinases are major effectors of Ras GTPases and key components of the transcriptional response to serum factors, acting at least in part through the extracellular signal-regulated...
Martins, L. Miguel, Morrison, Alastair, Klupsch, Kristina, Fedele, Valentina, Moisoi, Nicoleta, Teismann, Peter, ...
The serine protease HtrA2/Omi is released from the mitochondrial intermembrane space following apoptotic stimuli. Once in the cytosol, HtrA2/Omi has been implicated in promoting cell death by binding...
Monitoring conformational changes of proteins in cells by fluorescence lifetime imaging microscopy.
Calleja, Véronique, Ameer-Beg, Simon M, Vojnovic, Borivoj, Woscholski, Rudiger, Downward, Julian, Larijani, Banafshé
To be able to detect in situ changes in protein conformation without perturbing the physiological environment would be a major step forward in understanding the precise mechanism occurring in protein...
Ras protein regulation by G-protein-coupled receptors has been thought to occur through transactivation of receptor tyrosine kinases. New evidence suggests that these two receptor types independently...
Katso, Roy M., Pardo, Olivier E., Palamidessi, Andrea, Franz, Clemens M., Marinov, Marin, De Laurentiis, Angela, ...
Receptor-linked class I phosphoinositide 3-kinases (PI3Ks) induce assembly of signal transduction complexes through protein–protein and protein–lipid interactions that mediate cell proliferation,...
Suppression of Egr-1 transcription through targeting of the serum response factor by oncogenic H-Ras
Shin, Soon Young, Bahk, Young Yil, Ko, Jesang, Chung, Il-Yup, Lee, Young Seek, Downward, Julian, ...
The transcription factor Egr-1 functions as a key regulator in cellular growth, differentiation, and apoptosis. The loss of Egr-1 expression is closely associated with tumor development, although the...
Intramolecular and Intermolecular Interactions of Protein Kinase B Define Its Activation In Vivo
Calleja, Véronique, Alcor, Damien, Laguerre, Michel, Park, Jongsun, Vojnovic, Borivoj, Hemmings, Brian A, ...
Protein kinase B (PKB/Akt) is a pivotal regulator of diverse metabolic, phenotypic, and antiapoptotic cellular controls and has been shown to be a key player in cancer progression. Here, using...
Pardo, Olivier E, Wellbrock, Claudia, Khanzada, Umme K, Aubert, Muriel, Arozarena, Imanol, Davidson, Sally, ...
Patients with small cell lung cancer (SCLC) die because of chemoresistance. Fibroblast growth factor-2 (FGF-2) increases the expression of antiapoptotic proteins, XIAP and Bcl-XL, and triggers...
Induction of Mxi1-SRα by FOXO3a Contributes to Repression of Myc-Dependent Gene Expression▿ †
Delpuech, Oona, Griffiths, Beatrice, East, Philip, Essafi, Abdelkader, Lam, Eric W.-F., Burgering, Boudewijn, ...
Forkhead transcription factors of the O class (FOXOs) are important targets of the phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway. FOXOs have been implicated in the regulation of cell cycle...
Ahmed, Ahmed Ashour, Mills, Anthony D., Ibrahim, Ashraf E.K., Temple, Jillian, Blenkiron, Cherie, Vias, Maria, ...
The extracellular matrix (ECM) can induce chemotherapy resistance via AKT-mediated inhibition of apoptosis. Here, we show that loss of the ECM protein TGFBI (transforming growth factor beta induced)...
Vav3 Modulates B Cell Receptor Responses by Regulating Phosphoinositide 3-Kinase Activation
Inabe, Kazunori, Ishiai, Masamichi, Scharenberg, Andrew M., Freshney, Norman, Downward, Julian, Kurosaki, Tomohiro
To elucidate the mechanism(s) by which Vav3, a new member of the Vav family proteins, participates in B cell antigen receptor (BCR) signaling, we have generated a B cell line deficient in Vav3. Here...
Reynolds, Lucinda F., Smyth, Lesley A., Norton, Trisha, Freshney, Norman, Downward, Julian, Kioussis, Dimitris, ...
Vav1 is a signal transducing protein required for T cell receptor (TCR) signals that drive positive and negative selection in the thymus. Furthermore, Vav1-deficient thymocytes show greatly reduced...
Khwaja, Asim, Downward, Julian
Detachment of epithelial cells from the extracellular matrix leads to induction of programmed cell death, a process that has been termed “anoikis.” It has been reported recently that detachment...
Berrier, Allison L., Mastrangelo, Anthony M., Downward, Julian, Ginsberg, Mark, LaFlamme, Susan E.
Attachment of many cell types to extracellular matrix proteins triggers cell spreading, a process that strengthens cell adhesion and is a prerequisite for many adhesion-dependent processes including...
Janda, Elzbieta, Lehmann, Kerstin, Killisch, Iris, Jechlinger, Martin, Herzig, Michaela, Downward, Julian, ...
Multistep carcinogenesis involves more than six discrete events also important in normal development and cell behavior. Of these, local invasion and metastasis cause most cancer deaths but are the...
PINK1 Is Necessary for Long Term Survival and Mitochondrial Function in Human Dopaminergic Neurons
Wood-Kaczmar, Alison, Gandhi, Sonia, Yao, Zhi, Abramov, Andrey S. Y., Miljan, Erik A., Keen, Gregory, ...
Parkinson's disease (PD) is a common age-related neurodegenerative disease and it is critical to develop models which recapitulate the pathogenic process including the effect of the ageing process....