Source:http://linkedlifedata.com/resource/pubmed/id/17681949
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
39
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pubmed:dateCreated |
2007-9-24
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pubmed:abstractText |
The family of SLPs (Src homology 2 domain-containing leukocyte adaptor proteins) are cytoplasmic signal effectors of lymphocyte antigen receptors. A main function of SLP is to orchestrate the assembly of Ca(2+)-mobilizing enzymes at the inner leaflet of the plasma membrane. For this purpose, SLP-76 in T cells utilizes the transmembrane adaptor LAT, but the mechanism of SLP-65 membrane anchoring in B cells remains an enigma. We now employed two genetic reconstitution systems to unravel structural requirements of SLP-65 for the initiation of Ca(2+) mobilization and subsequent activation of gene transcription. First, mutational analysis of SLP-65 in DT40 B cells revealed that its C-terminal Src homology 2 domain controls efficient tyrosine phosphorylation by the kinase Syk, plasma membrane recruitment, as well as downstream signaling to NFAT activation. Second, we dissected these processes by expressing SLP-65 in SLP-76-deficient T cells and found that a kinase-independent adaptor function of Syk is required to link phosphorylated SLP-65 to Ca(2+) mobilization. These approaches unmask a mechanistic complexity of SLP-65 activation and coupling to signaling cascades in that Syk is upstream as well as downstream of SLP-65. Moreover, membrane anchoring of the SLP-65-assembled Ca(2+) initiation complex, which appears to be fundamentally different from that of closely related SLP-76, does not necessarily involve a B cell-specific component.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/B cell linker protein,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/LAT protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/SLP-76 signal Transducing adaptor...,
http://linkedlifedata.com/resource/pubmed/chemical/Syk kinase
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
29059-66
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:17681949-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:17681949-B-Lymphocytes,
pubmed-meshheading:17681949-Calcium,
pubmed-meshheading:17681949-Calcium Signaling,
pubmed-meshheading:17681949-Cell Membrane,
pubmed-meshheading:17681949-Enzyme Activation,
pubmed-meshheading:17681949-Humans,
pubmed-meshheading:17681949-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:17681949-Jurkat Cells,
pubmed-meshheading:17681949-Membrane Proteins,
pubmed-meshheading:17681949-Mutation,
pubmed-meshheading:17681949-NFATC Transcription Factors,
pubmed-meshheading:17681949-Phosphoproteins,
pubmed-meshheading:17681949-Phosphorylation,
pubmed-meshheading:17681949-Protein-Tyrosine Kinases,
pubmed-meshheading:17681949-T-Lymphocytes,
pubmed-meshheading:17681949-src Homology Domains
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pubmed:year |
2007
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pubmed:articleTitle |
SLP-65 signal transduction requires Src homology 2 domain-mediated membrane anchoring and a kinase-independent adaptor function of Syk.
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pubmed:affiliation |
Georg August University of Göttingen, Institute of Cellular & Molecular Immunology, Humboldtallee 34, 37073 Göttingen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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