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Journal Article

SLP-65 phosphorylation dynamics reveals a functional basis for signal integration by receptor-proximal adaptor proteins.

MPS-Authors
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Grønborg,  M.
Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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

/persons/resource/persons15947

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

External Ressource
Fulltext (public)

641646.pdf
(Publisher version), 885KB

Supplementary Material (public)

641646-Suppl-1.pdf
(Supplementary material), 3MB

641646-Suppl-2.pdf
(Supplementary material), 4MB

641646-Suppl-3.pdf
(Supplementary material), 141KB

641646-Suppl-4.pdf
(Supplementary material), 438KB

641646-Suppl-5.pdf
(Supplementary material), 45KB

641646-Suppl-6.pdf
(Supplementary material), 11KB

641646-Suppl-7.xls
(Supplementary material), 69KB

641646-Suppl-8.xls
(Supplementary material), 44KB

Citation

Oellerich, T., Grønborg, M., Neumann, K., Hsiao, H. H., Urlaub, H., & Wienands, J. (2009). SLP-65 phosphorylation dynamics reveals a functional basis for signal integration by receptor-proximal adaptor proteins. Molecular and Cellular Proteomics, 8(7), 1738-1750. doi:10.1074/mcp.M800567-MCP200.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-9352-D
Abstract
Understanding intracellular signal transduction by cell surface receptors requires information about the precise order of relevant modifications on the early transducer elements. Here we introduce the B cell line DT40 and its genetically engineered variants as a model system to determine and functionally characterize post-translational protein modifications in general. This is accomplished by a customized strategy that combines mass spectrometric analyses of protein modifications with subsequent mutational studies. When applied to the B cell receptor (BCR)-proximal effector SLP-65, this approach uncovered a differential and highly dynamic engagement of numerous newly identified phospho-acceptor sites. Some of them serve as kinase substrates in resting cells and undergo rapid dephosphorylation upon BCR ligation. Stimulationinduced phosphorylation of SLP-65 can be early and transient, or early and sustained, or late. Functional elucidation of conspicuous phosphorylation at serine 170 in SLP-65 revealed a BCR-distal checkpoint for some but not all possible B cell responses. Our data show that SLP-65 phosphorylation acts upstream for signal initiation and also downstream during selective processing of the BCR signal. Such a phenomenon defines a receptor-specific signal integrator.