rdf:type |
|
lifeskim:mentions |
umls-concept:C0034790,
umls-concept:C0037083,
umls-concept:C0039194,
umls-concept:C0205314,
umls-concept:C0679622,
umls-concept:C0679932,
umls-concept:C1167622,
umls-concept:C1421567,
umls-concept:C1527940,
umls-concept:C1533157,
umls-concept:C1705831,
umls-concept:C1719914,
umls-concept:C1999216,
umls-concept:C2828406
|
pubmed:issue |
2
|
pubmed:dateCreated |
1995-2-13
|
pubmed:abstractText |
Signaling by the T cell antigen receptor (TCR) is mediated by 17-residue tyrosine-based activation motifs (TAM) present in the cytoplasmic tails of the TCR zeta and CD3 chains. TAMs become tyrosine-phosphorylated upon TCR stimulation, creating a high affinity binding site for the tandem SH2 domains of ZAP-70. In permeabilized T cells, the association of TCR and ZAP-70 was inhibited by a protein tyrosine phosphatase (PTPase)-resistant TAM peptide analog, in which difluorophosphonomethyl phenylalanyl (F2Pmp) residues replaced phosphotyrosine. Inhibition of this association prevented TCR-stimulated tyrosine phosphorylation of ZAP-70 and reduced ZAP-70 kinase activity to basal levels. The reduction in ZAP-70 activity coincided with reduced tyrosine phosphorylation of a number of substrates. Such PTPase-resistant peptides, capable of disrupting SH2 domain-mediated protein-protein interactions, should prove useful in further dissection of multiple signaling pathways and may serve as models for rationally designed chemotherapeutic agents for the treatment of autoimmune and neoplastic disorders.
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Jan
|
pubmed:issn |
0021-9258
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:day |
13
|
pubmed:volume |
270
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
944-8
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:7822334-Amino Acid Sequence,
pubmed-meshheading:7822334-Cells, Cultured,
pubmed-meshheading:7822334-Humans,
pubmed-meshheading:7822334-Molecular Sequence Data,
pubmed-meshheading:7822334-Peptides,
pubmed-meshheading:7822334-Phosphorylation,
pubmed-meshheading:7822334-Protein Binding,
pubmed-meshheading:7822334-Protein-Tyrosine Kinases,
pubmed-meshheading:7822334-Receptors, Antigen, T-Cell,
pubmed-meshheading:7822334-Signal Transduction,
pubmed-meshheading:7822334-T-Lymphocytes,
pubmed-meshheading:7822334-Tyrosine,
pubmed-meshheading:7822334-ZAP-70 Protein-Tyrosine Kinase
|
pubmed:year |
1995
|
pubmed:articleTitle |
F2(Pmp)2-TAM zeta 3, a novel competitive inhibitor of the binding of ZAP-70 to the T cell antigen receptor, blocks early T cell signaling.
|
pubmed:affiliation |
Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|