Linked Life Data

10952971

Source:http://linkedlifedata.com/resource/pubmed/id/10952971

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
2001-1-18
pubmed:abstractText
Subcellular localization of cyclic nucleotide phosphodiesterases (PDEs) may be important in compartmentalization of cAMP/cGMP signaling responses. In 3T3-L1 adipocytes, mouse (M) PDE3B was associated with the endoplasmic reticulum (ER) as indicated by its immunofluorescent colocalization with the ER protein BiP and subcellular fractionation studies. In transfected NIH 3006 or COS-7 cells, recombinant wild-type PDE3A and PDE3B isoforms were both found almost exclusively in the ER. The N-terminal portion of PDE3 can be arbitrarily divided into region 1 (aa 1-300), which contains a large hydrophobic domain with six predicted transmembrane helices, followed by region 2 (aa 301-500) containing a smaller hydrophobic domain (of approximately 50 aa). To investigate the role of regions 1 and 2 in membrane association, we examined the subcellular localization of a series of catalytically active, Flag-tagged N-terminal-truncated human (H) PDE3A and MPDE3B recombinants, as well as a series of fragments from regions 1 and 2 of MPDE3B synthesized as enhanced green fluorescent (EGFP) fusion proteins in COS-7 cells. In COS-7 cells, the localization of a mutant HPDE3A, lacking the first 189 amino acids (aa) and therefore four of the six predicted transmembrane helices (H3A-Delta189), was virtually identical to that of the wild type. M3B-Delta302 (lacking region 1) and H3A-Delta397 (lacking region 1 as well as part of region 2) retained, to different degrees, the ability to associate with membranes, albeit less efficiently than H3A-Delta189. Proteins that lacked both regions 1 and 2, H3A-Delta510 and M3B-Delta604, did not associate with membranes. Consistent with these findings, region 1 EGFP-MPDE3B fusion proteins colocalized with the ER, whereas region 2 EGFP fusion proteins were diffusely distributed. Thus, some portion of the N-terminal hydrophobic domain in region 1 plus a second domain in region 2 are important for efficient membrane association/targeting of PDE3.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38749-61
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10952971-3',5'-Cyclic-AMP Phosphodiesterases, pubmed-meshheading:10952971-3T3 Cells, pubmed-meshheading:10952971-Adipocytes, pubmed-meshheading:10952971-Amino Acid Sequence, pubmed-meshheading:10952971-Animals, pubmed-meshheading:10952971-Base Sequence, pubmed-meshheading:10952971-COS Cells, pubmed-meshheading:10952971-Cell Line, pubmed-meshheading:10952971-Cercopithecus aethiops, pubmed-meshheading:10952971-Cyclic Nucleotide Phosphodiesterases, Type 3, pubmed-meshheading:10952971-DNA Primers, pubmed-meshheading:10952971-Endoplasmic Reticulum, pubmed-meshheading:10952971-Golgi Apparatus, pubmed-meshheading:10952971-Humans, pubmed-meshheading:10952971-Intracellular Membranes, pubmed-meshheading:10952971-Isoenzymes, pubmed-meshheading:10952971-Mice, pubmed-meshheading:10952971-Molecular Sequence Data, pubmed-meshheading:10952971-Protein Structure, Secondary, pubmed-meshheading:10952971-Recombinant Fusion Proteins, pubmed-meshheading:10952971-Sequence Deletion, pubmed-meshheading:10952971-Transfection
pubmed:year
2000
pubmed:articleTitle
Membrane localization of cyclic nucleotide phosphodiesterase 3 (PDE3). Two N-terminal domains are required for the efficient targeting to, and association of, PDE3 with endoplasmic reticulum.
pubmed:affiliation
Pulmonary/Critical Care Medicine Branch and Pathology Section, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't