Linked Life Data

11185568

Source:http://linkedlifedata.com/resource/pubmed/id/11185568

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-1-19
pubmed:abstractText
We have previously demonstrated that Galpha(s) associates with the juxtamembrane region of the epidermal growth factor (EGF) receptor (EGFR) and that the EGFR can phosphorylate and activate this G protein (H. Poppleton et al., 1996, J. Biol. Chem. 271, 6947-6951; H. Sun et al., 1995, Proc. Natl. Acad. Sci. USA 92, 2229-2233). In this report, we have employed peptides EGFR-13 and EGFR-14 (corresponding to amino acids 645-657 and 679-692 in the EGFR, respectively) which disrupt the association of Galpha(s) with the EGFR to investigate whether or not this region of the EGFR is required for phosphorylation of the G protein. EGFR-13 increased the tyrosine phosphorylation of G(alpha)s by two-fold whereas EGFR-14 decreased the phosphorylation of the G protein. Phosphorylation of EGFR-13 on the threonine residue corresponding to Thr654 of the EGFR obliterated the ability of the peptide to increase Galpha(s) phosphorylation. EGFR-13 and EGFR-14, but not phospho-EGFR-13, competed for the association of the EGFR with Galpha(s). A peptide betaIII-2 corresponding to amino acids Arg259-Lys273 in the beta2-adrenergic receptor which competes for association of Galpha(s) with the EGFR and increases protein tyrosine kinase activity of the EGFR could mimic the effects of EGFR-13. Among the three peptides (EGFR-13, EGFR-14, and betaIII-2) that interfere with association of Galpha(s) to the EGFR, only EGFR-13 and betaIII-2 have been shown to activate the G protein. Polylysine which increases EGFR tyrosine kinase activity but does not interfere with association of Galpha(s) and EGFR also augmented phosphorylation of Galpha(s) by the EGFR. Phosphopeptide mapping demonstrated that EGFR-13 and polylysine increased phosphorylation of Galpha(s) by the EGFR on the same additional sites. Collectively, these data suggest that the interaction of Galpha(s) with residues 645-657 of the EGFR, or a peptide corresponding to this sequence alters the conformation of the G protein and/or the EGFR such that Galpha(s) is readily phosphorylated by the EGFR. The peptide EGFR-14, which does not activate Galpha(s), does not allow for the efficient phosphorylation of the G protein even though it does elevate the intrinsic tyrosine kinase activity of the EGFR. The hyperphosphorylation of Galpha(s) by EGFR is likely to require the contact of the G protein with EGFR-13 region (aa 645-657 in the EGFR) as well as augmentation of EGFR kinase activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0003-9861
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
383
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
309-17
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11185568-Amino Acids, pubmed-meshheading:11185568-Dose-Response Relationship, Drug, pubmed-meshheading:11185568-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:11185568-Escherichia coli, pubmed-meshheading:11185568-Heterotrimeric GTP-Binding Proteins, pubmed-meshheading:11185568-Humans, pubmed-meshheading:11185568-Intracellular Membranes, pubmed-meshheading:11185568-Models, Biological, pubmed-meshheading:11185568-Peptide Mapping, pubmed-meshheading:11185568-Peptides, pubmed-meshheading:11185568-Phosphorylation, pubmed-meshheading:11185568-Plasmids, pubmed-meshheading:11185568-Polylysine, pubmed-meshheading:11185568-Protein Binding, pubmed-meshheading:11185568-Protein Conformation, pubmed-meshheading:11185568-Protein Structure, Tertiary, pubmed-meshheading:11185568-Protein-Tyrosine Kinases, pubmed-meshheading:11185568-Receptor, Epidermal Growth Factor, pubmed-meshheading:11185568-Receptors, Adrenergic, beta-2, pubmed-meshheading:11185568-Recombinant Proteins, pubmed-meshheading:11185568-Threonine, pubmed-meshheading:11185568-Tumor Cells, Cultured, pubmed-meshheading:11185568-Tyrosine
pubmed:year
2000
pubmed:articleTitle
The juxtamembrane region of the epidermal growth factor receptor is required for phosphorylation of Galpha(s).
pubmed:affiliation
Department of Pharmacology, University of Tennessee, The Center for Health Sciences, Memphis 38163, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't