Linked Life Data

11952788

Source:http://linkedlifedata.com/resource/pubmed/id/11952788

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2002-4-15
pubmed:abstractText
The human multidrug resistance protein 2 (MRP2, symbol ABCC2) is a polytopic membrane glycoprotein of 1545 amino acids which exports anionic conjugates across the apical membrane of polarized cells. A chimeric protein composed of C-proximal MRP2 and N-proximal MRP1 localized to the apical membrane of polarized Madin-Darby canine kidney cells (MDCKII) indicating involvement of the carboxy-proximal part of human MRP2 in apical sorting. When compared to other MRP family members, MRP2 has a seven-amino-acid extension at its C-terminus with the last three amino acids (TKF) comprising a PDZ-interacting motif. In order to analyze whether this extension is required for apical sorting of MRP2, we generated MRP2 constructs mutated and stepwise truncated at their C-termini. These constructs were fused via their N-termini to green fluorescent protein (GFP) and were transiently transfected into polarized, liver-derived human HepG2 cells. Quantitative analysis showed that full-length GFP-MRP2 was localized to the apical membrane in 73% of transfected, polarized cells, whereas it remained on intracellular membranes in 27% of cells. Removal of the C-terminal TKF peptide and stepwise deletion of up to 11 amino acids did not change this predominant apical distribution. However, apical localization was largely impaired when GFP-MRP2 was C-terminally truncated by 15 or more amino acids. Thus, neither the PDZ-interacting TKF motif nor the full seven-amino-acid extension were necessary for apical sorting of MRP2. Instead, our data indicate that a deletion of at least 15 C-terminal amino acids impairs the localization of MRP2 to the apical membrane of polarized cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1866-76
pubmed:dateRevised
2007-7-23
pubmed:meshHeading
pubmed-meshheading:11952788-Amino Acid Sequence, pubmed-meshheading:11952788-Animals, pubmed-meshheading:11952788-Base Sequence, pubmed-meshheading:11952788-Cell Line, pubmed-meshheading:11952788-DNA, Complementary, pubmed-meshheading:11952788-DNA Primers, pubmed-meshheading:11952788-Dogs, pubmed-meshheading:11952788-Drug Resistance, Multiple, pubmed-meshheading:11952788-Endocytosis, pubmed-meshheading:11952788-Green Fluorescent Proteins, pubmed-meshheading:11952788-Humans, pubmed-meshheading:11952788-Luminescent Proteins, pubmed-meshheading:11952788-Membrane Transport Proteins, pubmed-meshheading:11952788-Microscopy, Fluorescence, pubmed-meshheading:11952788-Molecular Sequence Data, pubmed-meshheading:11952788-Multidrug Resistance-Associated Proteins, pubmed-meshheading:11952788-Recombinant Fusion Proteins, pubmed-meshheading:11952788-Sequence Homology, Amino Acid
pubmed:year
2002
pubmed:articleTitle
Structural requirements for the apical sorting of human multidrug resistance protein 2 (ABCC2).
pubmed:affiliation
Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany. a.nies@dkfz.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't