Linked Life Data

14660637

Source:http://linkedlifedata.com/resource/pubmed/id/14660637

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2004-2-23
pubmed:abstractText
Peptides corresponding to residues 65-79 of human lymphocyte antigen class II sequence (DQA*03011) are cell-permeable and at high concentrations block activation of protein kinase B/Akt and p70-S6 kinase in T-cells, effects attributed to inhibition of phosphoinositide (PI) 3-kinase activity. To understand the molecular basis of this, we analyzed the effect this peptide had on activity of class I PI 3-kinases. Although there was no effect on the activity of class Ib PI 3-kinase or on the protein kinase activity of class I PI 3-kinases, there was a biphasic effect on lipid kinase activity of the class Ia enzymes. There was an inhibition of activity at higher peptide concentrations because of a formation of insoluble complexes between peptide and enzyme. Conversely, at lower peptide concentrations there was a profound activation of PI 3-kinase activity of class Ia PI 3-kinases. Studies of peptide variants revealed that all active peptides conform to heptad repeat motifs characteristic of coiled-coil helices. Surface plasmon resonance studies confirmed direct sequence-specific binding of active peptide to the p85alpha adapter subunit of class Ia PI 3-kinase. Active peptides also activated protein kinase B and extracellular signal-regulated kinase (ERK) in vivo in a wortmannin-sensitive manner while reducing recoverable cellular p85 levels. These results indicate that the human lymphocyte antigen class II-derived peptides regulate PI 3-kinase by direct interaction, probably via the coiled-coil domain. These peptides define a novel mechanism of regulating PI 3-kinase and will provide a useful tool for specifically dissecting the function of class Ia PI 3-kinase in cells and for probing structure-function relationships in the class Ia PI 3-kinase heterodimers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7505-11
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:14660637-Amino Acid Sequence, pubmed-meshheading:14660637-Animals, pubmed-meshheading:14660637-Binding Sites, pubmed-meshheading:14660637-CHO Cells, pubmed-meshheading:14660637-Cricetinae, pubmed-meshheading:14660637-Dose-Response Relationship, Drug, pubmed-meshheading:14660637-Enzyme Activation, pubmed-meshheading:14660637-Histocompatibility Antigens Class II, pubmed-meshheading:14660637-Mitogen-Activated Protein Kinases, pubmed-meshheading:14660637-Molecular Sequence Data, pubmed-meshheading:14660637-Phosphatidylinositol 3-Kinases, pubmed-meshheading:14660637-Protein-Serine-Threonine Kinases, pubmed-meshheading:14660637-Proto-Oncogene Proteins, pubmed-meshheading:14660637-Proto-Oncogene Proteins c-akt, pubmed-meshheading:14660637-Recombinant Proteins, pubmed-meshheading:14660637-Sequence Homology, pubmed-meshheading:14660637-Surface Plasmon Resonance
pubmed:year
2004
pubmed:articleTitle
Direct interaction of major histocompatibility complex class II-derived peptides with class Ia phosphoinositide 3-kinase results in dose-dependent stimulatory effects.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't