Linked Life Data

8740973

Source:http://linkedlifedata.com/resource/pubmed/id/8740973

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-1-27
pubmed:abstractText
Epidermal growth factor (EGF) stimulates cellular mitogenesis by binding to and activating its membrane-associated receptor. An important component of signal transduction by the activated receptor is the stimulation of an intrinsic tyrosyl residue-specific protein kinase, which selectively phosphorylates tyrosyl residues in the cytoplasmic tail of the receptor and in other cytoplasmic substrates. A recent study utilizing tyrsub, a new high affinity synthetic peptide substrate for the EGF receptor kinase, provided evidence that in peptide substrate binding, the tyrosyl residue plays the central role in recognition, with residues surrounding the tyrosyl residue contributing to stabilization of docking [Guyer et al. (1994) Arch. Biochem. Biophys. 312, 573-578]. A large body of previous work had identified acidic residues near the site of phosphorylation as most important for binding; therefore, other residues in tyrsub appeared to be promising sites for locating spectroscopic reporter groups. Since tyrsub has neutral residues -4 and +4 residues from the site of phosphorylation, we prepared two analogs of tyrsub, in each of which one of those residues was substituted with Cys. These cystyrsubs were found to be effectively phosphorylated by EGF receptor prepared from A431 cells, on stimulation with EGF, with high affinities [Km(app) = 40-50 microM.] Modification of the cystyrsubs with iodoacetamide had no deleterious effect on the ability of the peptide to be phosphorylated by the EGF receptor kinase, while the labeling by 5-iodoacetimidofluorescein completely abolished the productive interaction between the peptide and the EGF receptor. This unexpected failure of the fluorescently labeled peptides to be phosphorylated does, however, provide information on steric limitations to recognition of substrates by the EGF receptor kinase.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0367-8377
pubmed:author
pubmed:issnType
Print
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
219-26
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Steric constraints in the recognition of peptide substrates for the epidermal growth factor receptor kinase.
pubmed:affiliation
Department of Molecular Biology, Vanderbilt University, Nashville, Tennessee, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.