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

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.

Source: Signal Transduction Knowledge Environment - May 11, 2021 Category: Science Authors: Scheffler, L., Feicht, S., Babushku, T., Kuhn, L. B., Ehrenberg, S., Frankenberger, S., Lehmann, F. M., Hobeika, E., Jungnickel, B., Baccarini, M., Bornkamm, G. W., Strobl, L. J., Zimber-Strobl, U. Tags: STKE Research Articles Source Type: news