Prof. Dr. Bettina Warscheid
AG Biochemie und Funktionelle Proteomik
Institut für Biologie II and
BIOSS Centre for Biological Signalling Studies
Dissecting Signaling Complexes and Dynamic Changes of the B cell
B-cell activation as well as hyperactivity and autoimmunity of B cells involve the concerted action of proteins assembled into specific signalling complexes. Single complexes are further integrated into larger protein networks that allow to rapidly transduce signals from the receptor located at the cell surface into the nucleus. Aberrant B-cell receptor (BCR) signalling is often associated with autoimmune diseases and B-cell lymphomas. To obtain a better understanding of B-cell-associated signalling events, we will perform quantitative proteomics studies to dissect signalling complexes in resting and activated B cells. We will delineate the interactomes of the focal adhesion kinase (FAK) and the related proline-rich tyrosine kinase 2 (Pyk2) as well as the BCR/cytoskeleton interactome. Furthermore, we will define the protein complexes and dynamic phosphorylation profiles of cluster of differentiation 22 (CD22) and sialic-acid binding immunoglobulin-like lectin G (Siglec-G), two inhibitory receptors modulating the activity of B lymphocytes. State-of-the-art high resolution mass spectrometry (MS) will further be used to identify chaperone-mediated autophagy substrates in B cells and to study posttranslational modifications of B-cell-associated signalling factors beyond phosphorylation. A pulsed stable isotope labelling with amino acids (SILAC) approach will be employed to identify miR-148a targets in B cells. Moreover, we will develop a label-free MS method to perform large-scale quantitative proteomics of primary B cells. We will use this strategy to reveal how signal transducer and activator of transcription 6 (STAT6) regulates the murine B-cell proteome following the infection of mice with Nippostrongylus brasiliensis. Through integration of large-scale quantitative proteome and transcriptome data, we expect to expand our knowledge about ill-defined processes involved in germinal centre formation following helminth infection. Proteomics studies will be performed in close cooperation with several groups (e.g. P02, P03, P04, P05, P09, P20) in the TRR130.
Dalle Pezze, P., Ruf, S., Sonntag, A.G., Langelaar-Makkinje, M., Hall, P., Heberle, A.M., Navas, P.R., van Eunen, K., Tölle, R.C., Schwarz, J.J., Wiese, H., Warscheid, B., Deitersen, J., Storck, B., Fäßler, E., Schäuble, S., Hahn, U., Horvatovich, P., Shanley, D.P., and K. Thedieck (2016). A systems study on amino acid stimulation reveals concurrent activation of AMPK and mTOR converging on ULK1 and autophagy. Nat Commun in press.
Fischer, A., Brummer, T., Warscheid, B., and Radziwill, G. (2015). Differential tyrosine phosphorylation controls the function of CNK1 as a molecular switch in signal transduction, Biochim Biophys Acta 1853, 2847-55.
Hannemann, L., Suppanz I., Ba, Q., MacInnes, K., Drepper, F., Warscheid, B., and Koch, H.-G. (2016) Redox-activation of the universally conserved ATPase YchF by thioredoxin 1, Antioxid Redox Signal, 24, 141-156.
Hünten, S., Kaller, M., Drepper, F., Oeljeklaus, S., Bonfert, T., Ehrhart, F., Dueck, A., Eichner, N., Friedel, C., Meister, G., Zimmer, R., Warscheid, B., and Hermeking, H. (2015). p53-regulated networks of protein, mRNA, miRNA and lncRNA expression revealed by integrated pSILAC and NGS analyses, Mol Cell Proteomics 14, 2609-2629.
Kaller, M., Oeljeklaus, S., Warscheid, B.*, and Hermeking, H.* (2014). Identification of microRNA targets by pulsed SILAC. Methods Mol Biol 1188, 327-349. *shared senior authorship
Schwarz, J., Wiese, H., Tölle, R.C., Zarei, M., Dengjel J., Warscheid, B.*, and Thedieck, K.* (2015) Identification of acinus L as a novel mTORC1 substrate and mTOR interactor by a combined quantitative phosphoproteomics and interactomics approach, Mol Cell Proteomics 8, 2042-2055. *shared last authorship
Wiese, H., Kuhlmann, K., Wiese, S., Stoepel, N.S., Pawlas, M., Meyer, H.E., Stephan, C., Eisenacher, M., Drepper, F., Warscheid, B. (2014). Comparison of alternative MS/MS and bioinformatics approaches for confident phosphorylation site localization. J Proteome Res 13, 1128-1137.
Wiese, H., Gelis, L., Wiese, S., Reichenbach, C., Jovancevic, N., Osterloh, M., Meyer, H.E., Neuhaus, E.M., Hatt, H.H., Radziwill, G. and Warscheid, B. (2015). Quantitative phosphoproteomics reveals the protein tyrosine kinase Pyk2 as a central effector of olfactory receptor signaling in prostate cancer cells. Biochim Biophys Acta 1854, 632-640.