Linked Life Data

11891219

Source:http://linkedlifedata.com/resource/pubmed/id/11891219

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2002-5-20
pubmed:databankReference
pubmed:abstractText
We have cloned a novel adapter protein containing Src homology 2 and Src homology 3 domains similar to the Src family of tyrosine kinases. This molecule lacks a catalytic tyrosine kinase domain and is related to a previously identified protein, Src-like adapter protein (SLAP), and is therefore designated SLAP-2. Northern blot analysis indicates that SLAP-2 is predominantly expressed in the immune system. Jurkat T cells express SLAP-2 protein and overexpression of SLAP-2 in these cells negatively regulates T cell receptor signaling as assessed by interleukin-2 promoter or NF-AT promoter reporter constructs. Mutational analysis revealed that an intact SH2 domain of SLAP-2 is essential for this inhibitory effect, whereas mutation of the SH3 domain alone has no effect. This inhibitory effect is upstream of the activation of Ras and increase of intracellular calcium levels, as no inhibition was observed when the cells were activated by phorbol ester plus ionomycin. SLAP-2 interacts with Cbl in vivo in a phosphorylation independent manner and with ZAP-70 and T cell receptor zeta chain upon T cell receptor activation. Finally, we show that the mutation of a predicted myristoylation site within the NH(2)-terminal of SLAP-2 is essential for its inhibitory effect. This report therefore implicates SLAP and SLAP-2 as a family of adapter proteins that negatively regulate T cell receptor signaling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19131-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11891219-Adaptor Proteins, Signal Transducing, pubmed-meshheading:11891219-Amino Acid Sequence, pubmed-meshheading:11891219-Cloning, Molecular, pubmed-meshheading:11891219-DNA, Complementary, pubmed-meshheading:11891219-Humans, pubmed-meshheading:11891219-Jurkat Cells, pubmed-meshheading:11891219-Molecular Sequence Data, pubmed-meshheading:11891219-Myristic Acid, pubmed-meshheading:11891219-Phosphorylation, pubmed-meshheading:11891219-Proto-Oncogene Proteins pp60(c-src), pubmed-meshheading:11891219-RNA, Messenger, pubmed-meshheading:11891219-Receptors, Antigen, T-Cell, pubmed-meshheading:11891219-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11891219-Signal Transduction, pubmed-meshheading:11891219-Tyrosine, pubmed-meshheading:11891219-src Homology Domains
pubmed:year
2002
pubmed:articleTitle
A novel Src homology 2 domain-containing molecule, Src-like adapter protein-2 (SLAP-2), which negatively regulates T cell receptor signaling.
pubmed:affiliation
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't