Linked Life Data

11752646

Source:http://linkedlifedata.com/resource/pubmed/id/11752646

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
75
pubmed:dateCreated
2001-12-25
pubmed:abstractText
Once thought to be promiscuous killers, it is now known that natural killer (NK) cells possess an elaborate array of receptors that regulate NK cytotoxic and secretory functions upon interaction with target cell MHC class I proteins. These receptors, known as killer cell immunoglobulin-like receptors (KIRs) in humans, and Ly49 receptors in the mouse, have become the focus of intense study in an effort to discern the underlying biology of these large receptor families. These receptor families include both inhibitory and activating receptors. Interrogation of a target expressing KIR ligands leads to coengagement of the inhibitory receptor with as-yet poorly defined activation receptors. Kinases activated during engagement mediate the phosphorylation of the KIR or Ly49 cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The phosphorylated ITIMs serve as efficient recruitment points for the cytosolic protein tyrosine phosphatases, SHP-1 and SHP-2, resulting in the dephosphorylation of substrates critical for cellular activation. In contrast, some KIRs and Ly49s lack the ITIM and possess a charged residue in their transmembrane domains that mediates interaction with the DAP12 signal transduction chain. DAP12 uses its cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM) to mediate cellular activation. Engagement of a DAP12 coupled KIR or Ly49 results in phosphorylation of DAP12, and other key substrates, including the Syk tryosine kinase, phospholipase C, and c-Cbl. DAP12 activation then leads to the Mapk cascade and ultimately to enhanced degranulation, and production of cytokines and chemokines. Although the context in which inhibitory and activating KIR and Ly49s function is not yet known, the dissection of the activating and inhibitory signal transduction pathways should shed light on their method of integration into the activation sequela of NK cells. Ultimately, this work will lead to concrete understanding of the immunobiology of these seemingly antagonistic receptor systems.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1525-8882
pubmed:author
pubmed:issnType
Electronic
pubmed:day
27
pubmed:volume
2001
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
re1
pubmed:dateRevised
2009-10-21
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Intracellular signaling by the killer immunoglobulin-like receptors and Ly49.
pubmed:affiliation
Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute, NCI-FCRDC Building 560/Rm 31-93, Frederick, MD 21702, USA. McVicar@nih.gov
pubmed:publicationType
Journal Article, Review