Linked Life Data

7522165

Source:http://linkedlifedata.com/resource/pubmed/id/7522165

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1994-10-18
pubmed:abstractText
The recently characterized receptor for interleukin (IL)-7 (IL-7R) includes a unique alpha chain as well as a common gamma chain shared with the receptors for IL-2 and IL-4. Engagement of the IL-7R activates the intracellular enzyme phosphatidylinositol (PtdIns) 3-kinase but the mechanism of PtdIns 3-kinase activation and the molecular basis of its interaction with IL-7R are not known. Here we show that IL-7 causes the 85-kDa regulatory subunit of PtdIns 3-kinase (p85), and PtdIns 3-kinase activity, to associate with the IL-7R. This interaction can be ascribed to ligand-induced phosphorylation of a single Tyr residue in the receptor's unique alpha chain. Herbimycin A, a specific protein tyrosine kinase inhibitor, suppresses not only tyrosine phosphorylation of the IL-7R but also its association with p85. A phosphopeptide corresponding to the sequence surrounding Tyr449 in the cytoplasmic tail of the IL-7R alpha chain, but not its non-phosphorylated analogue or phosphopeptides coincident with the sequences surrounding other alpha chain Tyr residues, efficiently competes out p85 binding. Replacement of Tyr449 with Phe results in a loss of p85 binding. Finally, soluble forms of the src homology 2 domains of p85, which bind directly to phosphotyrosyl peptides, specifically inhibit the association of p85 with the IL-7R. Thus, PtdIns 3-kinase recruitment occurs through a single, phosphotyrosine dependent recognition motif surrounding Tyr449 in the IL-7R alpha chain. This motif corresponds to a canonical sequence for p85 binding, Tyr(P)-X-X-Met. Since the closely related IL-2R and IL-4R also activate PtdIns 3-kinase but are devoid of such canonical motifs, our results suggest that the mechanism by which IL-7R recruits and activates PtdIns 3-kinase differs fundamentally from that used by the other receptors. PtdIns 3-kinase may, therefore, play a unique and important role in the biological response to IL-7.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2168-74
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:7522165-Amino Acid Sequence, pubmed-meshheading:7522165-Animals, pubmed-meshheading:7522165-Enzyme Activation, pubmed-meshheading:7522165-Glutathione Transferase, pubmed-meshheading:7522165-Humans, pubmed-meshheading:7522165-Immunoblotting, pubmed-meshheading:7522165-Interleukin-7, pubmed-meshheading:7522165-Molecular Sequence Data, pubmed-meshheading:7522165-Phosphatidylinositol 3-Kinases, pubmed-meshheading:7522165-Phosphotransferases (Alcohol Group Acceptor), pubmed-meshheading:7522165-Phosphotyrosine, pubmed-meshheading:7522165-Precipitin Tests, pubmed-meshheading:7522165-Protein Binding, pubmed-meshheading:7522165-Receptors, Interleukin, pubmed-meshheading:7522165-Receptors, Interleukin-7, pubmed-meshheading:7522165-Recombinant Fusion Proteins, pubmed-meshheading:7522165-Tyrosine
pubmed:year
1994
pubmed:articleTitle
Interleukin-7 induces the association of phosphatidylinositol 3-kinase with the alpha chain of the interleukin-7 receptor.
pubmed:affiliation
Medical Research Council, Laboratory of Molecular Biology, Cambridge, GB.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't