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Cutting edge: Feed-forward activation of phospholipase C gamma 2 via C2 domain-mediated binding to SLP65.

MPS-Authors
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Hsiao,  H. H.
Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society;

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Urlaub,  H.
Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society;

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Griesinger,  C.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

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1877922_Suppl_1.pdf
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Citation

Engelke, M., Oellerich, T., Dittmann, K., Hsiao, H. H., Urlaub, H., Serve, H., et al. (2013). Cutting edge: Feed-forward activation of phospholipase C gamma 2 via C2 domain-mediated binding to SLP65. Journal of Immunology, 191(11), 5354-5358. doi:10.4049/jimmunol.1301326.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0014-CE0D-C
Abstract
Ag-mediated B cell stimulation relies on phospholipase C gamma 2 (PLC gamma 2) for Ca2+ mobilization. Enzymatic activity of PLC gamma 2 is triggered upon Src homology 2 domain-mediated binding to the tyrosine-phosphorylated adaptor SLP65. However, SLP65 phosphorylation outlasts the elevation of cytosolic Ca2+ concentration suggesting additional levels of PLC gamma 2 regulation. We show in this article that the functionality of the PLC gamma 2/SLP65 complex is controlled by the weakly characterized C2 domain of PLC gamma 2. Usually C2 domains bind membrane lipids, but that of PLC gamma 2 docks in a Ca2+-regulated manner to a distinct phosphotyrosine of SLP65. Hence, early Ca2+ fluxing provides feed-forward signal amplification by promoting anchoring of the PLC gamma 2 C2 domain to phospho-SLP65. As the cellular Ca2+ resources become exhausted, the concomitant decline of Ca2+ dampens the C2-phosphotyrosine interaction so that PLC gamma 2 activation terminates despite sustained SLP65 phosphorylation.