Linked Life Data

9382844

Source:http://linkedlifedata.com/resource/pubmed/id/9382844

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1998-2-19
pubmed:abstractText
A-kinase anchor protein 75 (AKAP75) binds regulatory subunits (RIIalpha and RIIbeta) of type II protein kinase A (PKAII) isoforms and targets the resulting complexes to sites in the cytoskeleton that abut the plasma membrane [1-7]. Co-localization of AKAP75-PKAII with adenylate cyclase and PKA substrate/effector proteins in cytoskeleton and plasma membrane effects a physical and functional integration of up-stream and downstream signaling proteins, thereby ensuring efficient propagation of signals carried by locally generated cyclic AMP (cAMP) [4-9]. An important, but previously untested, prediction of the AKAP model is that efficient, cyclic nucleotide-dependent liberation of diffusible PKA catalytic subunits from cytoskeleton-bound AKAP75-PKAII complexes will also enhance signaling to distal organelles, such as the nucleus. We tested this idea by suing HEK-A75 cells, in which PKAII isoforms are immobilized in cortical cytoskeleton by AKAP75. Abilities of HEK-A75 and control cells (with cytoplasmically dispersed PKAII isoforms) to respond to increases in cAMP content were compared. Cells with anchored PKAII exhibited a threefold higher level of nuclear catalytic subunit content and 4-10-fold greater increments in phosphorylation of a regulatory serine residue in cAMP response element binding protein (CREB) and in phosphoCREB-stimulated transcription of the c-fos gene. Each effect occurred more rapidly in cells containing targeted AKAP75-PKAII complexes. Thus, anchoring of PKAII in actin cortical cytoskeleton increases the rate, magnitude and sensitivity of cAMP signaling to the nucleus.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/8-((4-chlorophenyl)thio)cyclic-3',5'..., http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Thionucleotides
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0960-9822
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1011-4
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
A-kinase anchor protein 75 increases the rate and magnitude of cAMP signaling to the nucleus.
pubmed:affiliation
Department of Molecular Pharmacology, Atran Laboratories, Albert Einstein College of Medicine, Bronx, New York, New York 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't