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Identification of Ser/Thr phosphorylation sites in the C2-domain of phospholipase C γ2 (PLCγ2) using TRPM7-kinase

Cellular Signalling
DOI: 10.1016/j.cellsig.2012.06.015
  • Plcγ2
  • Ser
  • Thr Phosphorylation Trpm7
  • Hypomagnesia
  • B Cell Receptor Signaling


Abstract PLC-isozymes are central elements of cellular signaling downstream of numerous receptors. PLCγ2 is a pivotal component of B cell receptor (BCR) signaling. The regulation of PLCγ2-dependent signaling functions by Tyr-phosphorylation is well characterized, however, the potential role of Ser/Thr phosphorylation events remains undefined. TRPM7 is the fusion of a Ser/Thr kinase with an ion channel, and an essential component of Mg2+-homeostasis regulation. Although the interaction between the C2 domain of several PLC-isozymes and TRPM7 is well established, previous studies have focused on the effect of PLC-activity on TRPM7. Here, we investigated whether Ser/Thr phosphorylation sites in the C2 domain of PLCγ2 could be identified using TRPM7-kinase. We show that TRPM7-kinase phosphorylates PLCγ2 in its C2-domain at position Ser1164 and in the linker region preceding the C2-domain at position Thr1045. Using a complementation approach in PLCγ2−/− DT40 cells, we found that the PLCγ2-S1164A mutant fully restores BCR mediated Ca2+-responses under standard growth conditions. However, under hypomagnesic conditions, PLCγ2-S1164A fails to reach Ca2+-levels seen in cells expressing PLCγ2 wildtype. These results suggest that Mg2+-sensitivity of the BCR signaling pathway may be regulated by Ser/Thr phosphorylation of PLCγ2.

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