Linked Life Data

16431218

Source:http://linkedlifedata.com/resource/pubmed/id/16431218

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-1-24
pubmed:abstractText
We generated extracellular signal-regulated kinase 1/2 (ERK1/2) mutants by introducing a single amino-acid substitution in subdomain V of the catalytic domain and then examined the susceptibility of these mutants to PP1 derivatives originally designed as Src inhibitors. Substituting smaller amino acids (alanine [Ala (A)] or glycine [Gly (G)]) for glutamine [Gln (Q)] in subdomain V drastically increased the susceptibility of ERK1/2 to 1-naphthyl PP1 (1NA-PP1). Wild-type ERK1/2 was resistant to 1NA-PP1 inhibition. ERK1(Q122A) and ERK2(Q103A) were inhibited by 1NA-PP1 at IC(50) values of 1.7 +/- 0.13 and 2.1 +/- 0.18 microM, respectively. ERK1(Q122G) and ERK2(Q103G) were inhibited by 1NA-PP1 with IC(50) values of 3.6 +/- 0.26 and 18 +/- 2.2 microM, respectively. Other derivatives of PP1 (1-naphthylmethyl PP1 and 2-naphthylmethyl PP1) did not significantly inhibit ERK1/2 and its various mutants. In addition, these ERK1/2 mutants were activated by TPA when they were expressed in mammalian cells. These results suggest that the Gln residue of subdomain V is important in determining the susceptibility of ERK1/2 to 1NA-PP1 without significant changes in their enzymatic characteristics.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
341
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
261-5
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
A single amino-acid change in ERK1/2 makes the enzyme susceptible to PP1 derivatives.
pubmed:affiliation
Unit for Molecular Neurobiology of Learning and Memory, Initial Research Project, Okinawa Institute of Science and Technology, Uruma, Japan. sendo@irp.oist.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't