The multidrug resistance (mdr1) gene product functions as an ATP channel.
The multidrug resistance (mdr1) gene product, P-glycoprotein, is responsible for the ATP-dependent extrusion of a variety of compounds, including chemotherapeutic drugs, from cells. The data presented here show that cells with increased levels of the P-glycoprotein release ATP to the medium in proportion to the concentration of the protein in their plasma membrane. Furthermore, measurements of whole-cell and single-channel currents with patch-clamp electrodes indicate that the P-glycoprotein serves as an ATP-conducting channel in the plasma membrane. These findings suggest an unusual role for the P-glycoprotein.
Abraham
E H
EH
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
Prat
A G
AG
Gerweck
L
L
Seneveratne
T
T
Arceci
R J
RJ
Kramer
R
R
Guidotti
G
G
Cantiello
H F
HF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D016466:CHO Cells; D002462:Cell Membrane / Q000502:physiology; D006224:Cricetinae; D004351:Drug Resistance / Q000235:genetics*; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008175:Lung Neoplasms; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000906:Antibodies; D007473:Ion Channels; D008562:Membrane Glycoproteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D000255:Adenosine Triphosphate