Does B Cell Receptor Signaling in Chronic Lymphocytic Leukaemia Cells Differ from That in Other B Cell Types?
Figure 2
Signal integration following BCR engagement. Schematic of distal signaling events following BCR engagement. (a) Phospho-BLNK serves as a scaffold for Grb2, and this acts to prime activation of Sos. Active PKCβ phosphorylates RasGRP3 to facilitate its activation by DAG. The guanine exchange factor function of RasGRP3 converts GDP-Ras to GTP-Ras, which then acts to augment the guanine exchange factor function of Sos. Together RasGRP3 and Sos produce sufficient GTP-Ras to power activation of the MAPK cascade illustrated here by Raf, MEK, and ERK. (b) Active PKCβ acts to phosphorylate CARMA1 to induce assembly of the CARMA1-Bcl10-MALT1 complex. This allows activation of TAK1 which facilitates activation of the NFκB pathway by phosphorylating IKK and of the JNK pathway by phosphorylating MKK4 and MKK7. Active PKCβ also acts in a feedback inhibition loop by phosphorylating Btk on serine 180. This catalyzes the removal of Btk from the plasma membrane away from its substrate, PLCγ2.
