Linked Life Data

9099696

Source:http://linkedlifedata.com/resource/pubmed/id/9099696

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
1997-5-9
pubmed:databankReference
pubmed:abstractText
The cGMP-dependent protein kinases (cGK) Ialpha and Ibeta have identical cGMP binding sites and catalytic domains. However, differences in their first 100 amino acids result in 15-fold different activation constants for cGMP. We constructed chimeras to identify those amino acid sequences that contribute to the high affinity cGK Ialpha and low affinity cGK Ibeta phenotype. The cGK Ialpha/Ibeta chimeras contained permutations of six amino-terminal regions (S1-S6) including the leucine zipper (S2), the autoinhibitory domain (S4), and the hinge domain (S5, S6). The exchange of S2 along with S4 switched the phenotype from cGK Ialpha to cGK Ibeta and vice versa, suggesting that the domains with the highest homology between the two isozymes determine their affinity for cGMP. The high affinity cGK Ialpha phenotype was also obtained by a specific substitution within the hinge domain. Chimeras with the sequence of cGK Ialpha in S5 and cGK Ibeta in S6 were activated at up to 6-fold lower cGMP concentrations than cGK Ialpha. Based on the activation constants of all chimeras constructed, empirical weighting factors have been calculated that quantitatively describe the contribution of the individual amino-terminal domains S1-S6 to the high affinity cGK Ialpha phenotype.
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
18
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10522-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Identification of the amino acid sequences responsible for high affinity activation of cGMP kinase Ialpha.
pubmed:affiliation
Institut für Pharmakologie und Toxikologie der Technische Universität München, Biedersteiner Strasse 29, D-80802 München, Germany. ruth@ipt.med.tu-muenchen.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't