Linked Life Data

7509796

Source:http://linkedlifedata.com/resource/pubmed/id/7509796

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1994-4-1
pubmed:abstractText
The receptor tyrosine kinase c-kit is thought to mediate its diverse effects on different cell lineages by association and activation of distinct second messenger systems. One of the immediate events after binding of the kit ligand to the receptor is its association with the 85-kDa subunit (p85) of the phosphatidylinositol (PI) 3-kinase and the activation of the enzyme. In the present study, we examined the association and activation of PI 3-kinase with mutant forms of the c-kit receptor transiently expressed in COS-1 cells. To define the binding site of p85 we substituted the putative tyrosine phosphorylation sites in the kinase insert region of the c-kit receptor by phenylalanine (YF702, YF719, YF728, and YF745, respectively). The results indicate that, upon stimulation of cells with kit ligand, 1) the wild-type c-kit protein was readily autophosphorylated and autophosphorylation was not diminished significantly with any of the mutant proteins; 2) p85 and PI 3-kinase activity associated with wild-type c-Kit protein as well as with the mutant proteins YF702, YF728, and YF745. Ligand-induced association of p85 and PI 3-kinase activity were abolished with the YF719 c-Kit protein, and this was not due to different levels of expression of p85 or c-kit; and 3) c-kit receptor-bound p85 was not phosphorylated on tyrosine residues. These results indicate that tyrosine 719 within the 719YMDM motif in the kinase insert plays an important role in binding of p85 and that its phosphorylation is a prerequisite for binding of p85 and the subsequent activation of PI 3-kinase.
pubmed:grant
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
25
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6026-30
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Tyrosine residue 719 of the c-kit receptor is essential for binding of the P85 subunit of phosphatidylinositol (PI) 3-kinase and for c-kit-associated PI 3-kinase activity in COS-1 cells.
pubmed:affiliation
Molecular Biology Program, Sloan Kettering Institute, New York, New York.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't