Supplementary Figure 6: Signaling model comparing NBCs and GCBCs. | Nature Immunology

Supplementary Figure 6: Signaling model comparing NBCs and GCBCs.

From: The AKT kinase signaling network is rewired by PTEN to control proximal BCR signaling in germinal center B cells

Supplementary Figure 6

In comparison to NBCs, GCBCs express higher amounts of PTEN and PDK1, which changes the ratio of PtdIns(3,4,5)P3/ PtdIns(4,5)P2 and favors T308 over S473 phosphorylation on AKT. AKT, as differentially phosphorylated in GCBCs, in turn phosphorylates different substrates resulting in a GCBC-specific AKT signaling network. GCBC-specific AKT substrates include CSK, SHP-1 and HPK1, which when phosphorylated by AKT in GCBCs demonstrate enhanced activity that serves to inhibit upstream BCR signaling molecules such as Lyn, Syk and BLNK. This activation of regulators of proximal signaling further attenuates PtdIns(3,4,5)P3 generation. Taken together, this GCBC-specific feedback loop rewires BCR signaling, which can affect both GC selection and affinity maturation.

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