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Scheffler, L. ; Feicht, S. ; Babushku, T. ; Kuhn, L. ; Ehrenberg, S. ; Frankenberger, S. ; Lehmann, F.M. ; Hobeika, E.* ; Jungnickel, B. ; Baccarini, M.* ; Bornkamm, G.W. ; Strobl, L.J. ; Zimber-Strobl, U.

ERK phosphorylation is RAF independent in naïve and activated B cells but RAF dependent in plasma cell differentiation.

Sci. Signal. 14:eabc1648 (2021)
Postprint DOI PMC
Open Access Green
Members of the RAF family of serine-threonine kinases are intermediates in the mitogen-activated protein kinase and extracellular signal-regulated kinase (MAPK-ERK) signaling pathway, which controls key differentiation processes in B cells. By analyzing mice with B cell-specific deletion of Raf1, Braf, or both, we showed that Raf-1 and B-Raf acted together in mediating the positive selection of pre-B and transitional B cells as well as in initiating plasma cell differentiation. However, genetic or chemical inactivation of RAFs led to increased ERK phosphorylation in mature B cells. ERK activation in the absence of Raf-1 and B-Raf was mediated by multiple RAF-independent pathways, with phosphoinositide 3-kinase (PI3K) playing an important role. Furthermore, we found that ERK phosphorylation strongly increased during the transition from activated B cells to pre-plasmablasts. This increase in ERK phosphorylation did not occur in B cells lacking both Raf-1 and B-Raf, which most likely explains the partial block of plasma cell differentiation in mice lacking both RAFs. Collectively, our data indicate that B-Raf and Raf-1 are not necessary to mediate ERK phosphorylation in naïve or activated B cells but are essential for mediating the marked increase in ERK phosphorylation during the transition from activated B cells to pre-plasmablasts.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Mapk Pathway; Pro-b; Receptor; Kinase; Bcr; Signals; Dimerization; Inhibition; Dimers; Leads
ISSN (print) / ISBN 1945-0877
e-ISSN 1937-9145
Zeitschrift Science Signaling
Quellenangaben Band: 14, Heft: 682, Seiten: , Artikelnummer: eabc1648 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort 1200 New York Ave, Nw, Washington, Dc 20005 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Gene Vector (AGV)
Förderungen Deutsche Forschungsgemeinschaft (DFG)
Sander-Stiftung