Linked Life Data

11983694

Source:http://linkedlifedata.com/resource/pubmed/id/11983694

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
27
pubmed:dateCreated
2002-7-1
pubmed:abstractText
Previous studies have shown that exposure of cells to Zn2+ ions induces Ras and MAPK activation through the EGF receptor (EGFR). To further determine the role of EGFR in Zn2+-induced signaling, mouse B82L fibroblasts expressing no detectable EGFR protein (B82L-par), wild type EGFR (B82L-wt), kinase-deficient EGFR (B82L-K721M), or COOH-truncated EGFR (B82L-c'958) were tested. Exposure to Zn2+ induced Ras activity in B82L-wt, B82L-K721M, and B82L-c'958 but not in B82L-par cells, indicating that the tyrosine kinase domain and the auto-phosphorylation sites of the EGFR were not required for Zn2+-induced Ras activation. Zn2+ induced Src activation in all B82L cell lines, including B82L-par, indicating that Src activation is independent of the presence of the EGFR. A Src kinase inhibitor blocked Zn2+-induced Ras activation in all the B82L cell lines capable of this response, suggesting the involvement of Src kinase in Zn2+-induced Ras activation via the EGFR. Zn2+ induced the association of the EGFR with Src and specifically increased the phosphorylation of EGFR at tyrosine 845 (Tyr-845), a known Src phosphorylation site. Stably transfected B82L cells with a point mutation of the EGFR at Tyr-845 (B82L-Y845F) exhibited only basal Ras activity following exposure to Zn2+. These data demonstrate that Src-dependent phosphorylation of the EGFR at Tyr-845 is required for EGFR transactivation and Zn2+-induced Ras activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
24252-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Src-dependent phosphorylation of the epidermal growth factor receptor on tyrosine 845 is required for zinc-induced Ras activation.
pubmed:affiliation
Center for Environmental Medicine and Lung Biology, the Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.