Linked Life Data

8702998

Source:http://linkedlifedata.com/resource/pubmed/id/8702998

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
36
pubmed:dateCreated
1996-10-10
pubmed:abstractText
The proto-oncogene c-Cbl was originally identified as a cellular homologue of the transforming protein expressed by the murine Cas NS-1 retrovirus. The full-length c-Cbl protein is a predominantly cytoplasmic protein, abundant in lymphoid cells, and potentially involved in signal transduction in several cell types. The specific signal transduction pathways in which c-Cbl participates, and its precise role in these pathways, are unclear. Previous studies from our laboratory have shown that c-Cbl is the predominant tyrosine-phosphorylated protein bound to the p85 subunit of phosphatidylinositol (PI) 3-kinase on T lymphocyte and B lymphocyte activation. To further understand the properties of c-Cbl and the significance of its interactions with PI 3-kinase, we have further studied the cellular biological and biochemical responses of c-Cbl to stimulation in lymphoid cells. We show that stimulation induces the association of a highly tyrosine-phosphorylated pool of c-Cbl with lymphocyte membranes and with a detergent-insoluble particulate fraction. Immunoprecipitation of c-Cbl from subcellular fractions reveals that p85 is predominantly associated with the c-Cbl pool recovered from the membrane fraction, despite the fact that this pool represents a small amount of total cellular c-Cbl. The formation of c-Cbl.PI 3-kinase complexes on lymphocyte membranes did not depend on the catalytic activity of PI 3-kinase since it was unaltered by the treatment of cells with wortmannin prior to stimulation. Interestingly, c-Cbl tyrosine phosphorylation and the formation of c-Cbl.PI 3-kinase complexes were also observed in a mutant Jurkat cell line, JCaM1.6, lacking p56(lck) expression. Because p56(lck) is critical for mitogenic signal transduction in response to T cell receptor activation, our results suggest that the activation of c-Cbl and the formation of c-Cbl.PI 3-kinase complexes occur upstream or independently of mitogenic signal transduction pathways in T cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21939-43
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Formation of c-Cbl.phosphatidylinositol 3-kinase complexes on lymphocyte membranes by a p56lck-independent mechanism.
pubmed:affiliation
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.