Casein kinase I-dependent phosphorylation and stability of the yeast multidrug transporter Pdr5p.
The pleiotropic drug resistance protein, Pdr5p, is an ATP-binding cassette transporter of the plasma membrane of Saccharomyces cerevisiae. Overexpression of Pdr5p results in increased cell resistance to a variety of cytotoxic compounds, a phenotype reminiscent of the multiple drug resistance seen in tumor cells. Pdr5p and two other yeast ATP-binding cassette transporters, Snq2p and Yor1p, were found to be phosphorylated on serine residues in vitro. Mutations in the plasma membrane-bound casein kinase I isoforms, Yck1p and Yck2p, abolished Pdr5p phosphorylation and modified the multiple drug resistance profile. We showed Pdr5p to be ubiquitylated when overexpressed. However, instability of Pdr5p was only seen in Yck1p- and Yck2p-deficient strains, in which it was degraded in the vacuole via a Pep4p-dependent mechanism. Our results suggest that casein kinase I activity is required for membrane trafficking of Pdr5p to the cell surface. In the absence of functional Yck1p and Yck2p, Pdr5p is transported to the vacuole for degradation.
Decottignies
A
A
Unité de Biochimie Physiologique, Université Catholique de Louvain, Croix du Sud 2-20, B-1348 Louvain-la-Neuve, Belgium.
Owsianik
G
G
Ghislain
M
M
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000378:metabolism*; D047388:Casein Kinases; D002462:Cell Membrane / Q000737:chemistry; D018432:Drug Resistance, Multiple; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology*; D011755:Pyrophosphatases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D014452:Ubiquitins; D011494:Protein Kinases; D047388:Casein Kinases; D011755:Pyrophosphatases; C023278:uridine triphosphatase