Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
33
|
pubmed:dateCreated |
1988-12-20
|
pubmed:abstractText |
Cyclic nucleotide binding and activation properties of cAMP-dependent protein kinases from five independent mutants of S49 mouse lymphoma cells were studied. These mutants were all hemizygous for expression of mutant regulatory (R) subunits of the type I kinase with lesions that altered the electrostatic charge of R subunit: lesions in three of the mutants mapped to cAMP-binding site A, and those in two of the mutants mapped to cAMP-binding site B. A nucleotide mismatch assay using 32P-labeled cRNA and ribonuclease A confirmed and refined localization of the mutations to single amino acid residues implicated in cAMP binding. R subunits from all mutants retained the ability to bind cAMP, but binding behaved as if it were entirely to nonmutated sites: 1) relative affinities of 11 adenine-modified derivatives of cAMP for mutant enzymes were identical to their relative affinities for the site of wild-type kinase that corresponded to the nonmutated site of the mutant; 2) the potencies of these analogs as activators of mutant kinases were strictly correlated with their binding affinities (for wild-type enzyme activation potencies were correlated with mean affinities of the analogs for cAMP-binding sites A and B); 3) combinations of analogs with strong preferences for opposite cAMP-binding sites in wild-type kinase showed no synergism in activating mutant kinases; 4) dissociation of cAMP from mutant kinases was monophasic; and 5) high salt accelerated dissociation of cAMP from kinases with site B lesions but retarded dissociation from those with site A lesions.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Nov
|
pubmed:issn |
0021-9258
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
25
|
pubmed:volume |
263
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
17397-404
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:2846564-Amino Acid Sequence,
pubmed-meshheading:2846564-Animals,
pubmed-meshheading:2846564-Base Sequence,
pubmed-meshheading:2846564-Binding Sites,
pubmed-meshheading:2846564-Cell Line,
pubmed-meshheading:2846564-Cloning, Molecular,
pubmed-meshheading:2846564-Cyclic AMP,
pubmed-meshheading:2846564-DNA, Neoplasm,
pubmed-meshheading:2846564-Enzyme Activation,
pubmed-meshheading:2846564-Lymphoma,
pubmed-meshheading:2846564-Macromolecular Substances,
pubmed-meshheading:2846564-Molecular Sequence Data,
pubmed-meshheading:2846564-Mutation,
pubmed-meshheading:2846564-Protein Binding,
pubmed-meshheading:2846564-Protein Kinases
|
pubmed:year |
1988
|
pubmed:articleTitle |
Mutations that prevent cyclic nucleotide binding to binding sites A or B of type I cyclic AMP-dependent protein kinase.
|
pubmed:affiliation |
Cell Biology Research Group, University of Bergen, Norway.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|