Linked Life Data

9651683

Source:http://linkedlifedata.com/resource/pubmed/id/9651683

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1998-9-28
pubmed:abstractText
The c-kit-encoded receptor protein tyrosine kinase for stem cell factor (Kit/SCF-R) is essential for the development of cells within the hematopoietic, melanogenic and gametogenic lineages. SCF stimulation induces activation of phosphatidylinositol (PI) 3-kinase, which is required for SCF-induced mitogenesis and cell survival, and for activation of the serine/threonine, we found that, in response to SCF Akt became activated and mediated phosphorylation of Bad, a pro-apoptotic molecule, in a PI-3-kinase-dependent manner. Phosphorylation of Bad was restricted to Ser112 and Ser136 in vivo, but only the Akt phosphorylation sit Ser136 was essential for SCF-promoted cell survival. Furthermore, Bad and Akt interacted and colocalized in intact cells. A Kit/SCF-R gain-of-function mutant that has increased mitogenic and PI 3-kinase activation potential, due to the absence of the two protein kinase C negative feedback phosphorylation site, enhanced both Akt activation and Bad phosphorylation and also resulted in increased cell survival. Such a mechanism may account for how deregulated PI 3-kinase activity and naturally occurring gain-of-function point mutants of Kit/SCF-R lead to cellular transformation and fatal malignancies in man.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0960-9822
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
779-82
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
The kit receptor promotes cell survival via activation of PI 3-kinase and subsequent Akt-mediated phosphorylation of Bad on Ser136.
pubmed:affiliation
Molecular Biology and Virology Laboratory, Salk Institute, La Jolla, California 92037, USA. blume@salk.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't