Signaling Pathways Activated by the B-Cell Receptor in Chronic Lymphocytic Leukemia

Maria Teresa Scupoli; Giovanni Pizzolo


Expert Rev Hematol. 2012;5(3):341-348. 

In This Article

PLCγ2 Pathway

Activation of PLCγ2 by SYK, BTK and BLNK results in production of the second messenger, inositol-1,4,5-trisphosphate (IP3), and diacylglycerol (DAG), which lead to the subsequent increase in intracellular Ca2+ concentration and activation of PKC-β, respectively. PKCβ activity leads in turns to the activation of MAPKs, specifically, ERK, JNK and p38 MAPK.[14] PKC-β activity also induces phosphorylation and subsequent degradation of the NF-κB inhibitor (IκB), and thus activating NF-κB, which has important regulatory functions in B-cell activation, maturation and survival.[15] Increased intracellular Ca2+ concentration mediated by IP3 induces activation of nuclear factor of activated T cells (NFAT), a calcium-dependent transcription factor downstream of the calmodulin/calcineurin pathway involved in the development of mature B cells.[16]


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