title: Investigating RET RTK signaling pathways using an IAP-based activity-profiling approach.
abstract: Many neurodegenerative diseases, such as Parkinson's disease, can be directly correlated with the deregulation in neuronal signaling. Hence, it is indispensable for therapy development to understand the participating signaling processes. Because the activity of the involved protein kinases is of major interest for the investigation of these signaling processes, an affinity-based chemical proteomics approach that allows for the activity profiling of protein kinases was developed within this study. This approach was applied to investigate the RET9 receptor tyrosine kinase signaling pathway that plays a central role in neuronal signaling. In addition to already known RET9 downstream targets, several other protein kinases were found to be highly activated upon RET9 stimulation.
authors.affiliation: Organic and Bioorganic Chemistry, Department of Chemistry, Bielefeld University , Universitätsstraße 25, 33615 Bielefeld, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Höfener
authors.forename: Fiona
authors.initials: F
authors.lastname: Pachl
authors.forename: Tim
authors.initials: T
authors.lastname: Take
authors.forename: Gabriele
authors.initials: G
authors.lastname: Fischer von Mollard
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kuster
authors.forename: Norbert
authors.initials: N
authors.lastname: Sewald
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D020869:Gene Expression Profiling; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism*; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D053719:Tandem Mass Spectrometry; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D007093:Imidazoles; D011743:Pyrimidines; C115503:SB 218655; D011494:Protein Kinases; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D048051:p38 Mitogen-Activated Protein Kinases