Source:http://linkedlifedata.com/resource/pubmed/id/10358930
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1-2
|
pubmed:dateCreated |
1999-6-28
|
pubmed:abstractText |
Phosphoinositide 3-kinase (PI 3-kinase) is a key signaling enzyme implicated in a variety of receptor-stimulated cell responses. Stimulation of receptors possessing (or coupling to) protein-tyrosine kinase activates heterodimeric PI 3-kinases, which consist of an 85-kDa regulatory subunit (p85) containing Src-homology 2 (SH2) domains and a 110-kDa catalytic subunit (p110 alpha or p110 beta). Thus, this form of PI 3-kinases could be activated in vitro by a phosphotyrosyl peptide containing a YMXM motif that binds to the SH2 domains of p85. Receptors coupling to alpha beta gamma-trimeric G proteins also stimulate the lipid kinase activity of a novel p110 gamma isoform, which is not associated with p85, and thereby is not activated by tyrosine kinase receptors. The activation of p110 gamma PI 3-kinase appears to be mediated through the beta gamma subunits of the G protein (G beta gamma). In addition, rat liver heterodimeric PI 3-kinases containing the p110 beta catalytic subunit are synergistically activated by the phosphotyrosyl peptide plus G beta gamma. Such enzymatic properties were also observed with a recombinant p110 beta/p85 alpha expressed in COS-7 cells. In contrast, another heterodimeric PI 3-kinase consisting of p110 alpha and p85 in the same rat liver, together with a recombinant p110 alpha/p85 alpha, was not activated by G beta gamma, though their activities were stimulated by the phosphotyrosyl peptide. Synergistic activation of PI 3-kinase by the stimulation of the two major receptor types was indeed observed in intact cells, such as chemotactic peptide (N-formyl-Met-Leu-Phe) plus insulin (or Fc gamma II) receptors in differentiated THP-1 and CHO cells and adenosine (A1) plus insulin receptors in rat adipocytes. Thus, PI 3-kinase isoforms consisting of p110 beta catalytic and SH2-containing (p85 or its related) regulatory subunits appeared to function as a 'cross-talk' enzyme between the two signal transduction pathways mediated through tyrosine kinase and G protein-coupled receptors.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
|
pubmed:status |
MEDLINE
|
pubmed:month |
Apr
|
pubmed:issn |
0009-3084
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
98
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
79-86
|
pubmed:dateRevised |
2010-11-18
|
pubmed:meshHeading |
pubmed-meshheading:10358930-Amino Acid Sequence,
pubmed-meshheading:10358930-Animals,
pubmed-meshheading:10358930-GTP-Binding Proteins,
pubmed-meshheading:10358930-Humans,
pubmed-meshheading:10358930-Macromolecular Substances,
pubmed-meshheading:10358930-Models, Chemical,
pubmed-meshheading:10358930-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:10358930-Phosphotyrosine,
pubmed-meshheading:10358930-Rats,
pubmed-meshheading:10358930-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:10358930-Recombinant Proteins,
pubmed-meshheading:10358930-Signal Transduction,
pubmed-meshheading:10358930-src Homology Domains
|
pubmed:year |
1999
|
pubmed:articleTitle |
Synergistic activation of a family of phosphoinositide 3-kinase via G-protein coupled and tyrosine kinase-related receptors.
|
pubmed:affiliation |
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan. katada@mol.f.u-tokyo.ac.jp
|
pubmed:publicationType |
Journal Article,
Review,
Research Support, Non-U.S. Gov't
|