Cell Signal. 2012 Nov;24(11):2070-5. doi: 10.1016/j.cellsig.2012.06.015. Epub 2012 Jul 1.

Identification of Ser/Thr phosphorylation sites in the C2-domain of phospholipase C gamma2 (PLCgamma2) using TRPM7-kinase.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Deason-Towne, F., Perraud, A. L., Schmitz, C.,
["Department of Immunology, University of Colorado Denver, National Jewish Health, Denver, CO 80206, USA."]
PLC-isozymes are central elements of cellular signaling downstream of numerous receptors. PLCgamma2 is a pivotal component of B cell receptor (BCR) signaling. The regulation of PLCgamma2-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 Mg(2+)-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 PLCgamma2 could be identified using TRPM7-kinase. We show that TRPM7-kinase phosphorylates PLCgamma2 in its C2-domain at position Ser1164 and in the linker region preceding the C2-domain at position Thr1045. Using a complementation approach in PLCgamma2(-/-) DT40 cells, we found that the PLCgamma2-S1164A mutant fully restores BCR mediated Ca(2+)-responses under standard growth conditions. However, under hypomagnesic conditions, PLCgamma2-S1164A fails to reach Ca(2+)-levels seen in cells expressing PLCgamma2 wildtype. These results suggest that Mg(2+)-sensitivity of the BCR signaling pathway may be regulated by Ser/Thr phosphorylation of PLCgamma2.
PMID: 22759789External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Screening Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPM7 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PLCƣ2 Inference Prediction 22759789
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPM7 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PLCƣ2 Co-immunoprecipitation DT40 Mouse Full-length Not used 22759789
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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