Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2007-9-24
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29059-66
pubmed:dateRevised
2011-11-2
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
pubmed:year
2007
pubmed:articleTitle
SLP-65 signal transduction requires Src homology 2 domain-mediated membrane anchoring and a kinase-independent adaptor function of Syk.
pubmed:affiliation
Georg August University of Göttingen, Institute of Cellular & Molecular Immunology, Humboldtallee 34, 37073 Göttingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't