Linked Life Data

7737275

Source:http://linkedlifedata.com/resource/pubmed/id/7737275

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1995-6-7
pubmed:abstractText
The T cell molecule CD28 provides a co-stimulatory signal that is required for T cell proliferation, and has been implicated in the control of T cell anergy. An important clue to the signaling mechanism of CD28 is the finding that CD28 can bind to phosphatidylinositol 3-kinase (PI 3-kinase) by means of a cytoplasmic phospho-YMNM (pYMNM) motif. A remaining issue concerns whether CD28 can recruit other intracellular signaling molecules. In this study, we show that CD28 uses the same pYMNM motif to recruit a second intracellular protein, GRB-2. CD28-associated GRB-2, as detected by anti-GRB-2 immunoblotting, was found in human peripheral T cells, HPB-ALL and Jurkat cells. As in the case of PI3-kinase, antibody-induced cross-linking of CD28 induces a time-dependent recruitment of GRB-2. Likewise, mutation of the pY-191 residue within the pYMNM motif reduces GRB-2 binding. Peptide binding studies show that the SH2 domain of GRB-2 binds to the pYMNM motif with an affinity comparable to GRB-2/SHC, but some 10- to 100-fold lower than the CD28/PI 3-kinase. Despite this, CD28/GRB-2 and CD28/PI 3-kinase complexes are found to co-exist in peripheral T cells. Finally, immunoblotting shows that CD28 also associates with the gene product of the human homolog of the Drosophila Son of sevenless gene (SOS), a GRB-2-complexed guanine nucleotide exchange factor responsible for converting p21ras to a GTP-bound active state. CD28-associated GRB2/SOS is likely to serve an important link in the regulation of p21ras and lymphokine expression mediated by CD28.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1044-50
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:7737275-Adaptor Proteins, Signal Transducing, pubmed-meshheading:7737275-Amino Acid Sequence, pubmed-meshheading:7737275-Antigens, CD28, pubmed-meshheading:7737275-Binding Sites, pubmed-meshheading:7737275-GRB2 Adaptor Protein, pubmed-meshheading:7737275-Humans, pubmed-meshheading:7737275-Membrane Proteins, pubmed-meshheading:7737275-Molecular Sequence Data, pubmed-meshheading:7737275-Mutation, pubmed-meshheading:7737275-Proteins, pubmed-meshheading:7737275-Proto-Oncogene Proteins p21(ras), pubmed-meshheading:7737275-Second Messenger Systems, pubmed-meshheading:7737275-Sequence Analysis, pubmed-meshheading:7737275-Signal Transduction, pubmed-meshheading:7737275-Son of Sevenless Proteins, pubmed-meshheading:7737275-T-Lymphocytes, pubmed-meshheading:7737275-Tumor Cells, Cultured
pubmed:year
1995
pubmed:articleTitle
T cell antigen CD28 binds to the GRB-2/SOS complex, regulators of p21ras.
pubmed:affiliation
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't