Linked Life Data

11698416

Source:http://linkedlifedata.com/resource/pubmed/id/11698416

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-1-7
pubmed:abstractText
G proteins are critical cellular signal transducers for a variety of cell surface receptors. Both alpha and betagamma subunits of G proteins are able to transduce receptor signals. Several direct effect molecules for Gbetagamma subunits have been reported; yet the biochemical mechanism by which Gbetagamma executes its modulatory role is not well understood. We have shown that Gbetagamma could directly increase the kinase activity of Bruton's tyrosine kinase (Btk) whose defects are responsible for X chromosome-linked agammaglobulinemia in patients. The well characterized interaction of Gbetagamma with the PH (pleckstrin homology)/TH (Tec-homology) module of Btk was proposed to be the underlying activation mechanism. Here we show that Gbetagamma also interacts with the catalytic domain of Btk leading to increased kinase activity. Furthermore, we showed that the PH/TH module is required for Gbetagamma-induced membrane translocation of Btk. The membrane anchorage is also dependent on the interaction of Btk with phosphatidylinositol 3,4,5-trisphosphate, the product of phosphoinositide 3-kinase. These data support a dual role for Gbetagamma in the activation of Btk signaling function, namely membrane translocation and direct regulation of Btk catalytic activity.
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
11
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1488-92
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:11698416-Agammaglobulinemia, pubmed-meshheading:11698416-Animals, pubmed-meshheading:11698416-Biological Transport, pubmed-meshheading:11698416-Catalytic Domain, pubmed-meshheading:11698416-Cell Line, pubmed-meshheading:11698416-Culture Media, Serum-Free, pubmed-meshheading:11698416-Genes, Reporter, pubmed-meshheading:11698416-Heterotrimeric GTP-Binding Proteins, pubmed-meshheading:11698416-Humans, pubmed-meshheading:11698416-Microscopy, Fluorescence, pubmed-meshheading:11698416-Models, Biological, pubmed-meshheading:11698416-Phosphatidylinositol 3-Kinases, pubmed-meshheading:11698416-Protein Binding, pubmed-meshheading:11698416-Protein Subunits, pubmed-meshheading:11698416-Protein-Tyrosine Kinases, pubmed-meshheading:11698416-Recombinant Fusion Proteins, pubmed-meshheading:11698416-Signal Transduction
pubmed:year
2002
pubmed:articleTitle
G Protein beta gamma subunits act on the catalytic domain to stimulate Bruton's agammaglobulinemia tyrosine kinase.
pubmed:affiliation
Department of Physiology, Weill Medical College of Cornell University, New York, New York 10021, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't