Research team Dr. Michael Engelke
Research topic
Regulation of Ca2+ mobilization in activated B lymphocytes
The production of specific antibodies by B cells is a pivotal function of humoral immunity. For activation and development of B cells signals transduced by the B cell antigen receptor (BCR) are essential. Dysregulation of these signals can cause immunodeficiencies, autoimmunity, or tumor transformation.
Aim of our work is to decipher the regulation of BCR signals on a molecular level. Here, an important aspect is studying the kinetics and dynamics of signalling processes using live imaging techniques. In the recent years we elucidated the recruitment processes of different BCR effectors. Among others we found that already in resting cells important signalling complexes are pre-organized at vesicles.
In collaboration with Dr. Thomas Oellerich we study the dysregulation of so called tonic BCR signals that occur in absence of antigen-binding in B cell lymphomas. For this purpose we utilize quantitative mass spectrometry to comprehensively identify phosphor-proteins in cells. Recently, we could identify new BCR effectors that are essential for the survival of Burkitt’s lymphoma cells. This project may provide a basis for new cancer therapies.

MSc. Vanessa Kruse (PhD student)
Ines Heine (Technical Assistant)

Dr. Facundo Batista (London Research Institute, London)
Dr. Thomas Oellerich (Cambridge Institute of Medical Research, Cambridge; Universitätsklinikum Frankfurt)
Dr. Oliver Rocks (Max-Delbrück-Center, Berlin)
Dr. Henning Urlaub (MPI für biophysikalische Chemie, Göttingen)
Prof. Dr. Hubert Serve (Universitätsklinikum Frankfurt)





Manno B, Oellerich T, Schnyder T, Corso J, Lösing M, Neumann K, Urlaub H, Batista FD, Engelke M*, and Wienands J* (2016). The Dok-3/Grb2 adaptor module promotes inducible association of the lipid phosphatase SHIP with the BCR in a coreceptor-independent manner. European journal of immunology (accepted). *corresponding authors

Corso J, Pan KT, Walter R, Doebele C, Mohr S, Bohnenberger H, Ströbel P, Lenz C, Slabicki M, Hüllein J, Comoglio F, Rieger MA, Zenz T, Wienands J, Engelke M, Serve H, Urlaub H, Oellerich T (2016). Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival. Proc Natl Acad Sci USA. May 17;113(20):5688-93. [Pubmed]



Isernhagen A, Malzahn D, Viktorova E, Elsner L, Monecke S, von Bonin F, Kilisch M, Wermuth JM, Walther N, Balavarca Y, Stahl-Hennig C, Engelke M, Walter L, Bickeböller H, Kube D, Wulf G, Dressel R (2015). The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation. EMBO Mol Med. Oct 19;7(11):1480-502. [Pubmed]



Engelke M, Pirkuliyeva S, Kühn J, Wong L, Boyken J, Herrmann N, Becker S, Griesinger C, Wienands J (2014). Macromolecular assembly of the adaptor SLP-65 at intracellular vesicles in resting B cells. Science Signal. Aug 19; 7(339): ra79. [Pubmed]

Schneppenheim J, Hüttl S, Mentrup T, Lüllmann-Rauch R, Rothaug M, Engelke M, Dittmann K, Dressel R, Araki M, Araki K, Wienands J, Fluhrer R, Saftig P, Schröder B. (2014). The intramembrane proteases signal Peptide peptidase-like 2a and 2b have distinct functions in vivo. Mol Cell Biol. Apr;34(8):1398-411. [Pubmed]

Dieterle AM, Böhler P, Keppeler H, Alers S, Berleth N, Drießen S, Hieke N, Pietkiewicz S, Löffler AS, Peter C, Gray A, Leslie NR, Shinohara H, Kurosaki T, Engelke M, Wienands J, Bonin M, Wesselborg S, Stork B (2014). PDK1 controls upstream PI3K expression and PIP3 generation. Oncogene Jun;33(23):3043-53. [Pubmed]



Engelke M, Oellerich T, Dittmann K, Hsiao HH, Urlaub H, Serve H, Griesinger C, Wienands J. (2013). Cutting Edge: Feed-Forward Activation of Phospholipase Cγ2 via C2 Domain-Mediated Binding to SLP65.J Immunol. 191(11):5354-8. [Pubmed]

Dieterle AM, Böhler P, Keppeler H, Alers S, Berleth N, Drießen S, Hieke N, Pietkiewicz S, Löffler AS, Peter C, Gray A, Leslie NR, Shinohara H, Kurosaki T, Engelke M, Wienands J, Bonin M, Wesselborg S, Stork B (2013). PDK1 controls upstream PI3K expression and PIP3 generation. Oncogene Jul 29. [Epub ahead of print] [Pubmed]

König S, Regen T, Dittmann K, Engelke M, Wienands J, Schwendener R, Hanisch UK, Pukrop T, Hahn H (2013). Empty liposomes induce antitumoral effects associated with macrophage responses distinct from those of the TLR1/2 agonist Pam3CSK 4 (BLP). Cancer Immunol Immunother. 62(10):1587-1597.[Pubmed]

Castello A*, Gaya M, Tucholski J, Oellerich T, Lu KH, Tafuri A, Pawson T, Wienands J, Engelke M*, Batista FD* (2013). Nck-mediated recruitment of BCAP to the BCR regulates the PI(3)K-Akt pathway in B cells. Nat Immunol 14(9):966-975. *corresponding authors [Pubmed]

Oellerich T, Oellerich MF, Engelke M, Münch S, Mohr S, Nimz M, Hsiao HH, Corso J, Zhang J, Bohnenberger H, Berg T, Rieger MA, Wienands J, Bug G, Brandts C, Urlaub H, Serve H (2013).?2 integrin-derived signals induce cell survival and proliferation of AML blasts by activating a Syk/STAT signaling axis. Blood 121(19):3889-99. [Pubmed]

Schneppenheim J, Dressel R, Hüttl S, Lüllmann-Rauch R, Engelke M, Dittmann K, Wienands J, Eskelinen EL, Hermans-Borgmeyer I, Fluhrer R, Saftig P, Schröder B (2013). The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain. J Exp Med. 210(1):41-58. [Pubmed]

Lösing M, Goldbeck I, Manno B, Oellerich T, Schnyder T, Bohnenberger H, Stork B, Urlaub H, Batista FD, Wienands J, Engelke M (2013).The Dok-3/Grb2 protein signal module attenuates Lyn kinase-dependent activation of Syk kinase in B cell antigen receptor microclusters. J Biol Chem. 288(4):2303-13. [Pubmed]



Schrader A, Meyer K, von Bonin F, Vockerodt M, Walther N, Hand E, Ulrich A, Matulewicz K, Lenze D, Hummel M, Kieser A, Engelke M, Trümper L, Kube D (2012). Global gene expression changes of in vitro stimulated human transformed germinal centre B cells as surrogate for oncogenic pathway activation in individual aggressive B cell lymphomas. Cell Commun Signal 10(1):43. [Pubmed]

Junek S*, Engelke M*, Schild D, Wienands J (2012) (* contributed equally).Spatiotemporal resolution of Ca2+ signaling events by real time imaging of single B cells. FEBS Lett. 586(10):1452-8. [Pubmed]



Oellerich, T., Bremes, V., Neumann, K., Bohnenberger, H., Dittmann, K., Hsiao, H.H., Engelke, M., Schnyder, T., Batista, F.D., Urlaub, H., Wienands, J.(2011). The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85. Embo J 30: 3620-3634. [Pubmed]

Schnyder, T., Castello, A., Feest, C., Harwood, N.E., Oellerich, T., Urlaub, H., Engelke, M., Wienands, J., Bruckbauer, A., Batista, F.D. (2011). B cell receptor-mediated antigen gathering requires ubiquitin ligase Cbl and adaptors Grb2 and Dok-3 to recruit dynein to the signaling microcluster. Immunity 34: 905-918. [Pubmed]

Bohnenberger, H., Oellerich, T., Engelke, M., Hsiao, H.H., Urlaub, H., Wienands, J. Complex phosphorylation dynamics control the composition of the Syk interactome in B cells (2011). European journal of immunology 41: 1550-1562. [Pubmed]

Neumann, K., Oellerich, T., Heine, I., Urlaub, H., Engelke, M. (2011). Fc gamma receptor IIb modulates the molecular Grb2 interaction network in activated B cells. Cellular Signalling 23: 893-900. [Pubmed]



Borgerding, A., J. Hasenkamp, M. Engelke, N. Burkhart, L. Trumper, J. Wienands, and B. Glass (2010). B-lymphoma cells escape rituximab-triggered elimination by NK cells through increased HLA class I expression. Experimental Haematology 38:213-221. [Pubmed]

Rieke, C., Kahne, T., Schweitzer, K., Schraven, B., Wienands, J., Engelke, M. and Naumann, M. (2010). Non-T cell activation linker regulates ERK activation in Helicobacter pylori-infected epithelial cells. Cell Signal 22:395-403. [Pubmed]



Engels, N., Engelke, M., Wienands, J. (2008). Conformational plasticity and navigation of signaling proteins in antigen-activated B lymphocytes. Adv Immunology 97: 251-281. [Pubmed]

Engelke, M., Engels, N., Dittmann, K., Stork, B., Wienands, J. (2007). Ca2+ signaling in antigen receptor-activated B lymphocytes. Immunol Rev 218:235-246. [ Pubmed]

Stork, B., Neumann, K., Goldbeck, I., Alers, S., Kähne, T., Naumann, M., Engelke, M., Wienands, J. (2007). Subcellular localization of Grb2 by the adaptor protein Dok-3 restricts the intensity of Ca2+ signaling in B cells. Embo J 26:1140-1149.[Pubmed]

Stork, B.*, Engelke, M.*, Frey, J., Horejsí, V., Hamm-Baarke, A., Schraven, B., Kurosaki, T., Wienands, J (2004). (* contributed equally) Grb2 and the non-T cell activation linker NTAL constitute a Ca2+-regulating signal circuit in B lymphocytes. Immunity 21:681-691 (including cover page). [Pubmed]

Engelke, M., Friedrich O., Günther, U., Jüngling, E., Zitt, C., Lückhoff, A., Budde, P., Frey, J. (2002). Structural domains required for channel function of the mouse transient receptor potential protein homologue TRP1beta. FEBS Lett 523:193-199. [Pubmed]

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