Linked Life Data

15708852

Source:http://linkedlifedata.com/resource/pubmed/id/15708852

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2005-4-11
pubmed:abstractText
The epidermal growth factor receptor (EGFR) is activated by ionizing radiation (IR) in many human carcinomas, mediating a cytoprotective response and subsequent radioresistance. The underlying molecular mechanisms remain to be understood, and we propose here a specific role for the Tyr-992 residue of EGFR and examine its regulation by the phosphatase, SHP2. The -fold increase in phosphorylation of Tyr-992 in response to IR is twice that seen with ligand (EGF) binding. Mutation of Tyr-992 blocked completely IR-induced EGFR phosphorylation and reduced activation of the downstream signaling molecule, phospholipase Cgamma. IR has previously been demonstrated to inhibit activity of protein-tyrosine phosphatases. Following protein-tyrosine phosphatase inhibition by sodium vanadate both EGFR expressing Chinese hamster ovary (CHO) and A431 exhibited up to an 8-fold increase in the basal level of Tyr-992 phosphorylation, significantly higher than that seen with Tyr-1173, Tyr-1068, and total EGFR Tyr. CHO cells expressing a SHP2 mutant also demonstrated up to an 8-fold increase in the basal level of Tyr-992 phosphorylation. In this study we show the unique association of SHP2 with EGFR in response to IR, with up to a 2.5-fold increase in the direct association of endogenous SHP2 with EGFR-wt in response to 2 gray of IR in both CHO and A431 cells. Mutation of Tyr-992 abolished this response. In conclusion we have identified several differentially activated Tyr residues, one of which is not only more sensitive to activation by IR, translating into differential activation of downstream signaling, but uniquely modulated by the phosphatase SHP2.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14597-604
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15708852-Animals, pubmed-meshheading:15708852-Blotting, Western, pubmed-meshheading:15708852-CHO Cells, pubmed-meshheading:15708852-Cell Line, Tumor, pubmed-meshheading:15708852-Cricetinae, pubmed-meshheading:15708852-DNA Mutational Analysis, pubmed-meshheading:15708852-Dose-Response Relationship, Radiation, pubmed-meshheading:15708852-Humans, pubmed-meshheading:15708852-Immunoprecipitation, pubmed-meshheading:15708852-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:15708852-Kinetics, pubmed-meshheading:15708852-Ligands, pubmed-meshheading:15708852-Mutation, pubmed-meshheading:15708852-Phospholipase C gamma, pubmed-meshheading:15708852-Phosphorylation, pubmed-meshheading:15708852-Protein Tyrosine Phosphatase, Non-Receptor Type 11, pubmed-meshheading:15708852-Protein Tyrosine Phosphatases, pubmed-meshheading:15708852-Radiation, Ionizing, pubmed-meshheading:15708852-Receptor, Epidermal Growth Factor, pubmed-meshheading:15708852-Signal Transduction, pubmed-meshheading:15708852-Time Factors, pubmed-meshheading:15708852-Transfection, pubmed-meshheading:15708852-Type C Phospholipases, pubmed-meshheading:15708852-Tyrosine
pubmed:year
2005
pubmed:articleTitle
Requirement of Tyr-992 and Tyr-1173 in phosphorylation of the epidermal growth factor receptor by ionizing radiation and modulation by SHP2.
pubmed:affiliation
Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298-0058, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural