Linked Life Data

8509414

Source:http://linkedlifedata.com/resource/pubmed/id/8509414

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
1993-7-13
pubmed:abstractText
Cyclic AMP-dependent protein kinase II beta (PKAII beta) is the principal mediator of cAMP action in neurons. A Kinase Anchor Proteins (AKAPs) are enriched in forebrain neurons and have distinct high affinity binding domains for the regulatory subunit (RII beta) of PKAII beta and components of the dendritic cytoskeleton. The selective accumulation of AKAP.RII beta complexes near dendritic microtubules tethers PKAII beta in proximity with adenylate cyclase in the synaptic plasma membrane and cytoskeletal proteins that are substrates for the kinase, thereby creating intraneuronal target sites for signals carried by cAMP. We have characterized the targeting (anchoring) and tethering (RII beta binding) domains of a prototypic anchor protein AKAP75. Deletion of N-terminal residues 27-48 generated a truncated RII beta-binding protein that partitions equally between the cytosol and detergent-insoluble fractions of HEK293 cells. Further removal of a non-adjacent sequence (residues 77-91) produced a cytosolic protein with unimpaired RII beta binding activity. Thus, two noncontiguous domains mediate the intracellular localization of AKAP75. Boundaries for the RII beta tethering domain were mapped to residues 392-413 by scanning mutagenesis. Residues containing long aliphatic side chains are essential for the high affinity binding of RII beta by AKAP75. Contributions of hydrophobic amino acids to tethering activity also depend on the position of the residue in the sequence. Certain conservative mutations that should not alter significantly the overall hydrophobicity or helicity of the tethering region (e.g. replacement of Leu with Ala) diminish the RII beta binding activity of AKAP75.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
268
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12796-804
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:8509414-A Kinase Anchor Proteins, pubmed-meshheading:8509414-Adaptor Proteins, Signal Transducing, pubmed-meshheading:8509414-Amino Acid Sequence, pubmed-meshheading:8509414-Animals, pubmed-meshheading:8509414-Base Sequence, pubmed-meshheading:8509414-Brain, pubmed-meshheading:8509414-Carrier Proteins, pubmed-meshheading:8509414-Cattle, pubmed-meshheading:8509414-Cloning, Molecular, pubmed-meshheading:8509414-Cytoskeleton, pubmed-meshheading:8509414-DNA Mutational Analysis, pubmed-meshheading:8509414-Humans, pubmed-meshheading:8509414-Macromolecular Substances, pubmed-meshheading:8509414-Molecular Sequence Data, pubmed-meshheading:8509414-Mutagenesis, pubmed-meshheading:8509414-Mutagenesis, Insertional, pubmed-meshheading:8509414-Oligodeoxyribonucleotides, pubmed-meshheading:8509414-Oligonucleotides, Antisense, pubmed-meshheading:8509414-Polymerase Chain Reaction, pubmed-meshheading:8509414-Protein Kinases, pubmed-meshheading:8509414-Proteins, pubmed-meshheading:8509414-Restriction Mapping, pubmed-meshheading:8509414-Sequence Deletion, pubmed-meshheading:8509414-Sequence Homology, Amino Acid
pubmed:year
1993
pubmed:articleTitle
Characterization of distinct tethering and intracellular targeting domains in AKAP75, a protein that links cAMP-dependent protein kinase II beta to the cytoskeleton.
pubmed:affiliation
Department of Molecular Pharmacology, Atran Laboratories, Albert Einstein College of Medicine, Bronx, New York 10461.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't