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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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Mapk Pathway; Pro-b; Receptor; Kinase; Bcr; Signals; Dimerization; Inhibition; Dimers; Leads
ISSN (print) / ISBN 1945-0877
e-ISSN 1937-9145
Journal Science Signaling
Quellenangaben Volume: 14, Issue: 682, Pages: , Article Number: eabc1648 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place 1200 New York Ave, Nw, Washington, Dc 20005 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
Grants Deutsche Forschungsgemeinschaft (DFG)
Sander-Stiftung