@article{EisenhardtSprengerRoeringetal.2016,
  author    = {Eisenhardt, Anja E. and Sprenger, Adrian and R{\"o}ring, Michael and Herr, Ricarda and Weinberg, Florian and K{\"o}hler, Martin and Braun, Sandra and Orth, Joachim and Diedrich, Britta and Lanner, Ulrike and Tscherwinski, Natalja and Schuster, Simon and Dumaz, Nicolas and Schmidt, Enrico and Baumeister, Ralf and Schlosser, Andreas and Dengjel, J{\"o}rn and Brummer, Tilman},
  title     = {Phospho-proteomic analyses of B-Raf protein complexes reveal new regulatory principles},
  series = {Oncotarget},
  volume    = {7},
  journal   = {Oncotarget},
  number    = {18},
  doi       = {10.18632/oncotarget.8427},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166529},
  pages     = {26628-26652},
  year      = {2016},
  abstract  = {B-Raf represents a critical physiological regulator of the Ras/RAF/MEK/ERK-pathway and a pharmacological target of growing clinical relevance, in particular in oncology. To understand how B-Raf itself is regulated, we combined mass spectrometry with genetic approaches to map its interactome in MCF-10A cells as well as in B-Raf deficient murine embryonic fibroblasts (MEFs) and B-Raf/Raf-1 double deficient DT40 lymphoma cells complemented with wildtype or mutant B-Raf expression vectors. Using a multi-protease digestion approach, we identified a novel ubiquitination site and provide a detailed B-Raf phospho-map. Importantly, we identify two evolutionary conserved phosphorylation clusters around T401 and S419 in the B-Raf hinge region. SILAC labelling and genetic/biochemical follow-up revealed that these clusters are phosphorylated in the contexts of oncogenic Ras, sorafenib induced Raf dimerization and in the background of the V600E mutation. We further show that the vemurafenib sensitive phosphorylation of the T401 cluster occurs in trans within a Raf dimer. Substitution of the Ser/Thr-residues of this cluster by alanine residues enhances the transforming potential of B-Raf, indicating that these phosphorylation sites suppress its signaling output. Moreover, several B-Raf phosphorylation sites, including T401 and S419, are somatically mutated in tumors, further illustrating the importance of phosphorylation for the regulation of this kinase.},
  language  = {en}
}
@article{MaassDuezelBrigadskietal.2016,
  author    = {Maass, Anne and D{\"u}zel, Sandra and Brigadski, Tanja and Goerke, Monique and Becke, Andreas and Sobieray, Uwe and Neumann, Katja and L{\"o}vd{\´e}n, Martin and Lindenberger, Ulman and B{\"a}ckman, Lars and Braun-Dullaeus, R{\"u}diger and Ahrens, D{\"o}rte and Heinze, Hans-Jochen and M{\"u}ller, Notger G. and Lessmann, Volkmar and Sendtner, Michael and D{\"u}zel, Emrah},
  title     = {Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults},
  series = {NeuroImage},
  volume    = {131},
  journal   = {NeuroImage},
  doi       = {10.1016/j.neuroimage.2015.10.084},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189219},
  pages     = {142-154},
  year      = {2016},
  abstract  = {Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77 years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n = 21) or to a control group (indoor progressive-muscle relaxation/stretching, n = 19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here.},
  language  = {en}
}