Browsing
     by title


0-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

or enter first few letters:   
OK
Full Text
Peer Reviewed
See detailPhosphorylated HER-2 tyrosine kinase and Her-2/neu gene amplification as predictive factors of response to trastuzumab in patients with HER-2 overexpressing metastatic breast cancer (MBC).
Giuliani, Rosa; Durbecq, Virginie; Di Leo, Angelo et al

in European Journal of Cancer (2007), 43(4), 725-35

AIM: Trastuzumab (T), a humanised monoclonal antibody against HER-2, is active in HER-2-positive MBC patients. However, nearly 60% of the patients do not benefit from T, stressing the need for additional ... [more ▼]

AIM: Trastuzumab (T), a humanised monoclonal antibody against HER-2, is active in HER-2-positive MBC patients. However, nearly 60% of the patients do not benefit from T, stressing the need for additional predictive markers. The following markers could be implicated in response to T: (1) the magnitude of Her-2 gene amplification; (2) the co-expression of the other HER family receptors, possibly responsible for HER-2 trans-activation; (3) the activated status of HER-2; (4) the activated status of downstream effectors as mitogen-activated protein kinases (MAPKs), p38 and p27. METHODS: Medical files of patients with MBC treated with T either as a single agent or in combination with chemotherapy (CT) were reviewed. HER family members (EGFR, HER-2, HER-3, HER-4), the phosphorylated forms of EGFR (p-EGFR), HER-2 (p-HER-2) and of the downstream effectors were evaluated in the archival tumours. The correlation between clinical outcome and the expression of these markers was investigated. RESULTS: (1) Increasing values of Her-2 amplification were associated with a higher probability of achieving an objective response; (2) no statistical significant correlation between the expression of the HER family receptors was found; (3) p-HER-2 was predictive of response in patients treated with T+CT; (4) a statistically significant correlation between p-ERK 1/2, p-p38 and p-HER-2 emerged, pointing to the activated vertical pathway p-HER-2-->p-MAPKs. CONCLUSIONS: p-HER-2 and the magnitude of Her-2 amplification were predictive of response to T and their role deserves to be analysed in larger and more homogenous T-treated populations such as those from large phase III trials. [less ▲]

Detailed reference viewed: 12 (1 ULg)
Peer Reviewed
See detailPhosphorylated Thiamine Derivatives and Cortical Activity in the Baboon Papio Papio: Effect of Intermittent Light Stimulation
Bettendorff, Lucien ULg; Schoffeniels, Ernest; Naquet, R. et al

in Journal of Neurochemistry (1989), 53(1), 80-87

The effect of intermittent light stimulation (ILS) on the distribution of thiamine derivatives in three brain areas (occipital, motor, and premotor) was compared in photosensitive and nonphotosensitive ... [more ▼]

The effect of intermittent light stimulation (ILS) on the distribution of thiamine derivatives in three brain areas (occipital, motor, and premotor) was compared in photosensitive and nonphotosensitive baboons. ILS induces paroxysmal discharges in the motor and premotor areas of photosensitive animals only. In baboons submitted to ILS, thiamine triphosphate (TTP) decreases in both photosensitive and nonphotosensitive animals; thiamine monophosphate (TMP) increases in photosensitive animals, which present ILS-induced paroxysmal discharges, whereas it is unaffected in nonphotosensitive animals. The variations are the most significant in the occipital (visual) cortex. A consumption of TTP may result from electrical activity induced by light stimulation in the occipital area. No correlation between ILS-induced paroxysmal activity and a decrease in TTP contents was found. However, photosensitive animals are affected differently from nonphotosensitive animals, as their content of TMP in the cerebral cortex increases on stimulation. However, as long as the exact role of thiamine compounds in relation to membrane excitability in the nervous system remains unknown, it is impossible to conclude whether the differences observed in the metabolism of thiamine compounds are the cause or the consequence of the photosensitivity in the baboon Papio papio. [less ▲]

Detailed reference viewed: 14 (6 ULg)
Full Text
Peer Reviewed
See detailPhosphorylation At Ser244 By Ck1 Determines Nuclear Localization And Substrate Targeting Of Pkd2
Von Blume, J.; Knippschild, U.; Dequiedt, Franck ULg et al

in Embo Journal (2007), 26(22),

Protein kinase D2 (PKD2), a member of the PKD family of serine/threonine kinases, is localized in various subcellular compartments including the nucleus where the kinase accumulates upon activation of G ... [more ▼]

Protein kinase D2 (PKD2), a member of the PKD family of serine/threonine kinases, is localized in various subcellular compartments including the nucleus where the kinase accumulates upon activation of G-protein-coupled receptors. We define three critical post-translational modifications required for nuclear accumulation of PKD2 in response to activation of the CCK2 receptor (CCK2R): phosphorylation at Ser706 and Ser710 within the activation loop by PKC eta leading to catalytic activity and phosphorylation at Ser244 within the zinc-finger domain, which is crucial for blocking nuclear export of active PKD2 by preventing its interaction with the Crm-1 export machinery. We identify CK1delta and epsilon as upstream activated kinases by CCK2R that phosphorylate PKD2 at Ser244. Moreover, nuclear accumulation of active PKD2 is a prerequisite for efficient phosphorylation of its nuclear substrate, HDAC7. Only nuclear, active PKD2 mediates CCK2R-induced HDAC7 phosphorylation and Nur77 expression. Thus, we define a novel, compartment-specific signal transduction pathway downstream of CCK2R that phosphorylates PKD2 at three specific sites, results in nuclear accumulation of the active kinase and culminates in efficient phosphorylation of nuclear PKD2 substrates in human gastric cancer cells. [less ▲]

Detailed reference viewed: 10 (2 ULg)
Full Text
Peer Reviewed
See detailPhosphorylation of bovine leukemia virus Tax protein is required for in vitro transformation but not for transactivation.
Willems, Luc ULg; Grimonpont, Cathy; Kerkhofs, Pierre et al

in Oncogene (1998), 16(17), 2165-76

The Tax proteins of the oncovirinae viruses are phosphorylated transcriptional activators that exhibit oncogenic potential. The role of phosphorylation in their functional activities remains unknown. As a ... [more ▼]

The Tax proteins of the oncovirinae viruses are phosphorylated transcriptional activators that exhibit oncogenic potential. The role of phosphorylation in their functional activities remains unknown. As a model for the Human T-cell leukemia virus type I (HTLV-I), Bovine Leukemia Virus (BLV) permits the characterization of viral replication and leukemogenesis in vivo. Here, we show that the BLV Tax protein is phosphorylated on serine residues 106 and 293 both in insect and in mammalian cells. These sites can also be efficiently phosphorylated by the cdc2 and MAP kinases in vitro. Mutation of these residues does not affect the capacity of the Tax protein to function as a transactivator. Indeed, the Tax proteins mutated at one or both serines increase LTR-directed viral transcription at levels similar to those obtained with wild-type Tax in cell culture. Moreover, inhibition of Tax phosphorylation by W7, a calmodulin antagonist, does not alter its transactivation activity. Thus, phosphorylation on serines 106 and 293 is not required for transactivation by Tax. However, simultaneous substitution of both serines into alanine residues destroys the capacity of Tax to cooperate with the Ha-ras oncogene to transform primary rat embryo fibroblasts and induce tumors in nude mice. When the serines were replaced with aspartic acid residues, the oncogenic potential of Tax was maintained indicating that the negative charge rather than the phosphate group itself was required for Tax oncogenicity. Finally, to assess the role of the serine residues in vivo, recombinant viruses which express the Tax mutants were constructed and injected into sheep. It appeared that the mutated proviruses replicate at levels similar to the wild-type virus in vivo. We conclude that Tax phosphorylation is dispensable for transactivation and viral replication in vivo but is required for its oncogenic potential in vitro. [less ▲]

Detailed reference viewed: 34 (13 ULg)
Full Text
Peer Reviewed
See detailPhosphorylation Of Histone Deacetylase 7 By Protein Kinase D Mediates T Cell Receptor-Induced Nur77 Expression And Apoptosis
Dequiedt, Franck ULg; Van Lint, J.; Lecomte, E. et al

in Journal of Experimental Medicine (2005), 201(5),

Detailed reference viewed: 12 (4 ULg)
See detailPhosphorylation of huntingtin by cyclin dependent kinase 5.
Godin, Juliette ULg; Anne, Sandrine; Humbert, Sandrine

Poster (2008)

Detailed reference viewed: 4 (0 ULg)
Full Text
Peer Reviewed
See detailPhosphorylation of Neurogenin2 specifies the migration properties and the dendritic morphology of pyramidal neurons in the neocortex.
Hand, Randal; Bortone, Dante; Mattar, Pierre et al

in Neuron (2005), 48(1), 45-62

The molecular mechanisms specifying the dendritic morphology of different neuronal subtypes are poorly understood. Here we demonstrate that the bHLH transcription factor Neurogenin2 (Ngn2) is both ... [more ▼]

The molecular mechanisms specifying the dendritic morphology of different neuronal subtypes are poorly understood. Here we demonstrate that the bHLH transcription factor Neurogenin2 (Ngn2) is both necessary and sufficient for specifying the dendritic morphology of pyramidal neurons in vivo by specifying the polarity of its leading process during the initiation of radial migration. The ability of Ngn2 to promote a polarized leading process outgrowth requires the phosphorylation of a single tyrosine residue at position 241, an event that is neither involved in Ngn2 direct transactivation properties nor its proneural function. Interestingly, the migration defect observed in the Ngn2 knockout mouse and in progenitors expressing the Ngn2(Y241F) mutation can be rescued by inhibiting the activity of the small-GTPase RhoA in cortical progenitors. Our results demonstrate that Ngn2 coordinates the acquisition of the radial migration properties and the unipolar dendritic morphology characterizing pyramidal neurons through molecular mechanisms distinct from those mediating its proneural activity. [less ▲]

Detailed reference viewed: 21 (5 ULg)
Full Text
Peer Reviewed
See detailPhosphorylation of NF-kappa B and I kappa B proteins: implications in cancer and inflammation
Viatour, Patrick ULg; Merville, Marie-Paule ULg; Bours, Vincent ULg et al

in Trends in Biochemical Sciences (2005), 30(1), 43-52

Nuclear factor-kappaB (NF-kappaB) is a transcription factor that has crucial roles in inflammation, immunity, cell proliferation and apoptosis. Activation of NF-kappaB mainly occurs via IkappaB kinase ... [more ▼]

Nuclear factor-kappaB (NF-kappaB) is a transcription factor that has crucial roles in inflammation, immunity, cell proliferation and apoptosis. Activation of NF-kappaB mainly occurs via IkappaB kinase (IKK)-mediated phosphorylation of inhibitory molecules, including IkappaBalpha. Optimal induction of NF-kappaB target genes also requires phosphorylation of NF-kappaB proteins, such as p65, within their transactivation domain by a variety of kinases in response to distinct stimuli. Whether, and how, phosphorylation modulates the function of other NF-kappaB and IkappaB proteins, such as B-cell lymphoma 3, remains unclear. The identification and characterization of all the kinases known to phosphorylate NF-kappaB and IkappaB proteins are described here. Because deregulation of NF-kappaB and IkappaB phosphorylations is a hallmark of chronic inflammatory diseases and cancer, newly designed drugs targeting these constitutively activated signalling pathways represent promising therapeutic tools. [less ▲]

Detailed reference viewed: 36 (8 ULg)
Full Text
Peer Reviewed
See detailPhosphorylation of p65(RelA) on Ser547 by ATM represses NF-κB-dependent transcription of specific genes after genotoxic stress.
Sabatel, Hélène ULg; Di Valentin, Emmanuel ULg; Gloire, Geoffrey ULg et al

in PLoS ONE (2012)

The NF-κB pathway is involved in immune and inflammation responses, proliferation, differentiation and cell death or survival. It is activated by many external stimuli including genotoxic stress. DNA ... [more ▼]

The NF-κB pathway is involved in immune and inflammation responses, proliferation, differentiation and cell death or survival. It is activated by many external stimuli including genotoxic stress. DNA double-strand breaks activate NF-κB in an ATM-dependent manner. In this manuscript, a direct interaction between p65(RelA) and the N-terminal extremity of ATM is reported. We also report that only one of the five potential ATM-(S/T)Q target sites present in p65, namely Ser547, is specifically phosphorylated by ATM in vitro. A comparative transcriptomic analysis performed in HEK-293 cells expressing either wild-type HA-p65 or a non-phosphorylatable mutant HA-p65S547A identified several differentially transcribed genes after an etoposide treatment (e.g. IL8, A20, SELE). The transcription of these genes is increased in cells expressing the mutant. Substitution of Ser547 to alanine does not affect p65 binding abilities on the κB site of the IL8 promoter but reduces p65 interaction with HDAC1. Cells expressing p65S547A have a higher level of histone H3 acetylated on Lys9 at the IL8 promoter, which is in agreement with the higher gene induction observed. These results indicate that ATM regulates a sub-set of NF-κB dependent genes after a genotoxic stress by direct phosphorylation of p65. [less ▲]

Detailed reference viewed: 41 (17 ULg)
Peer Reviewed
See detailPhosphorylation of Proteins Induced in a Murine Pre-T Cell Line by Neurohypophysial Peptides
Martens, Henri ULg; Kecha, O.; Charlet-Renard, C. et al

in Advances in Experimental Medicine and Biology (1998), 449

Detailed reference viewed: 1 (0 ULg)
See detailPhosphorylation of proteins induced in a murine pre-T cell line by neurohypophysial peptides
Martens, Henri ULg; Kecha, Ouafae; Brilot, Fabienne et al

in Zingg, Hans H.; Bourque, Charles W.; Bichet, Daniel (Eds.) Vasopressin and Oxytocin: Molecular, Cellular, and Clinical Advances (1998)

Detailed reference viewed: 3 (0 ULg)
Full Text
Peer Reviewed
See detailPhosphorylation of SCG10/stathmin-2 determines multipolar stage exit and neuronal migration rate
Westerlund, N.; Zdrojewska, J.; Padzik, A. et al

in Nature Neuroscience (2011)

Detailed reference viewed: 20 (2 ULg)
Peer Reviewed
See detailPhosphorylation of the Bovine Leukemia Virus transactivator p34Tax is required for transformation but not for transactivation.
Kettmann, Richard ULg; Grimonpont, C.; Kerkhofs, Pierre et al

in FASEB Journal (1997), 11(9), 1179

Detailed reference viewed: 5 (1 ULg)
Full Text
Peer Reviewed
See detailPhosphorylation of varicella-zoster virus IE63 protein by casein kinases influences its cellular localization and gene regulation activity
Bontems, Sébastien ULg; Di Valentin, Emmanuel ULg; Baudoux, Laurence et al

in Journal of Biological Chemistry (2002), 277(23), 21050-21060

During the early phase of varicella-zoster virus (VZV) infection, Immediate Early protein 63 (IE63) is expressed rapidly and abundantly in the nucleus, while during latency, this protein is confined ... [more ▼]

During the early phase of varicella-zoster virus (VZV) infection, Immediate Early protein 63 (IE63) is expressed rapidly and abundantly in the nucleus, while during latency, this protein is confined mostly to the cytoplasm. Because phosphorylation is known to regulate many cellular events, we investigated the importance of this modification on the cellular localization of IE63 and on its regulatory properties. We demonstrate here that cellular casein kinases I and II are implicated in the in vitro and in vivo phosphorylation of IE63. A mutational approach also indicated that phosphorylation of the protein is important for its correct cellular localization in a cell type-dependent fashion. Using an activity test, we demonstrated that IE63 was able to repress the gene expression driven by two VZV promoters and that phosphorylation of the protein was required for its full repressive properties. Finally, we showed that IE63 was capable of exerting its repressive activity in the cytoplasm, as well as in the nucleus, suggesting a regulation at the transcriptional and/or post-transcriptional level. [less ▲]

Detailed reference viewed: 40 (15 ULg)
Full Text
Peer Reviewed
See detailPhosphorylation processes mediate rapid changes of brain aromatase activity
Balthazart, Jacques ULg; Baillien, M.; Ball, G. F.

in Journal of Steroid Biochemistry & Molecular Biology (2001), 79(1-5), 261-277

The enzyme aromatase (also called estrogen synthase) that catalyzes the transformation of testosterone (T) into estradiol plays a key limiting role in the action of T on many aspects of reproduction. The ... [more ▼]

The enzyme aromatase (also called estrogen synthase) that catalyzes the transformation of testosterone (T) into estradiol plays a key limiting role in the action of T on many aspects of reproduction. The distribution and regulation of aromatase in the quail brain has been studied by radioenzyme assays on microdissected brain areas, immunocytochemistry, RT-PCR and in situ hybridization. High levels of aromatase activity (AA) characterize the sexually dimorphic, steroid-sensitive medial preoptic nucleus (PONI), a critical site of T action and aromatization for the activation of male sexual behavior. The boundaries of the POM are clearly outlined by a dense population of aromatase-containing cells as visualized by both immunocytochemistry and in situ hybridization histochemistry. Aromatase synthesis in the POM is controlled by T and its metabolite estradiol, but estradiol receptors alpha (ERalpha) are not normally co-localized with aromatase in this brain area. Estradiol receptor beta (ERbeta) has been recently cloned in quail and localized in POM but we do not yet know whether ERbeta occurs in aromatase cells. It is therefore not known whether estrogens regulate aromatase synthesis directly or by affecting different inputs to aromatase cells as is the case with the gonadotropin releasing hormone neurons. The presence of aromatase in presynaptic boutons suggests that locally formed estrogens may exert part of their effects by non-genomic mechanisms at the membrane level. Rapid effects of estrogens in the brain that presumably take place at the neuronal membrane level have been described in other species. If fast transduction mechanisms for estrogen are available at the membrane level, this will not necessarily result in rapid changes in brain function if the availability of the ligand does not also change rapidly. We demonstrate here that AA in hypothalamic homogenates is rapidly down-regulated by exposure to conditions that enhance protein phosphorylation (addition of Ca2+, Mg2+, ATP). This inhibition is blocked by kinase inhibitors which supports the notion that phosphorylation processes are involved. A rapid (within minutes) and reversible regulation of AA is also observed in hypothalamic explants incubated in vitro and exposed to high Ca2+ levels (K+-induced depolarization, treatment by thapsigargin, by kainate, AMPA or NMDA). The local production and availability of estrogens in the brain can therefore be rapidly changed by Ca2+ based on variation in neurotransmitter activity. Locally-produced estrogens are as a consequence available for non-genomic regulation of neuronal physiology in a manner more akin to the action of a neuropeptide/neurotransmitter than previously thought. (C) 2002 Elsevier Science Ltd. All rights reserved. [less ▲]

Detailed reference viewed: 24 (0 ULg)
Full Text
Peer Reviewed
See detailA phosphorylation switch regulates the transcriptional activation of cell cycle regulator p21 by histone deacetylase inhibitors.
Simboeck, E.; Sawicka, A.; Zupkovitz, G. et al

in Journal of Biological Chemistry (2010)

Histone deacetylase inhibitors induce cell cycle arrest and apoptosis in tumor cells and are therefore promising anti-cancer drugs. The CDK inhibitor p21 is activated in HDAC inhibitor treated tumor cells ... [more ▼]

Histone deacetylase inhibitors induce cell cycle arrest and apoptosis in tumor cells and are therefore promising anti-cancer drugs. The CDK inhibitor p21 is activated in HDAC inhibitor treated tumor cells and its growth-inhibitory function contributes to the anti-tumorigenic effect of HDAC inhibitors. We show here that induction of p21 by trichostatin A involves MAP kinase signaling. Activation of the MAP kinase signaling pathway by growth factors or stress signals results in histone H3 serine 10 phosphorylation at the p21 promoter and is crucial for acetylation of the neighboring lysine 14 and recruitment of activated RNA polymerase II in response to trichostatin A treatment. In non-induced cells, the protein phosphatase PP2A is associated with the p21 gene and counteracts its activation. Induction of p21 is linked to simultaneous acetylation and phosphorylation of histone H3. The dual modification mark H3S10phK14ac at the activated p21 promoter is recognized by the phospho-binding protein 14-3-3 zeta, which protects the phosphoacetylation mark from being processed by PP2A. Taken together we have revealed a crosstalk of reversible phosphorylation and acetylation signals that controls the activation of p21 by HDAC inhibitors and identify the phosphatase PP2A as chromatin-associated transcriptional repressor in mammalian cells. [less ▲]

Detailed reference viewed: 20 (3 ULg)
Full Text
Peer Reviewed
See detailPhotic memory for executive brain responses
Chellappa*, Sarah Laxhmi ULg; Ly*, Julien ULg; Meyer, Christelle ULg et al

in Proceedings of the National Academy of Sciences of the United States of America (2014), Epub ahead of print

Detailed reference viewed: 21 (2 ULg)
See detailPhoto : EDDIE KIRKLAND
Sacré, Robert ULg

in Soul Bag (2000), (158), 25

Eddie Krkland, Peer juillet 1988

Detailed reference viewed: 14 (0 ULg)
Full Text
See detailLa (photo)production d'hydrogène par les microorganismes
Lecler, Renaud ULg

Conference (2011, April 04)

Detailed reference viewed: 61 (15 ULg)