In this report, the role of phosphorylation in the regulation of ubiquitination and turnover of the ABC-transporter Ste6 was investigated. We demonstrate that Ste6 is phosphorylated in vivo and that this phosphorylation is dependent on the presence of an acidic stretch ('A-box') in the linker region previously shown to be important for ubiquitination and fast turnover of Ste6. By mutagenesis, two serine/threonine residues were identified in the A-box region that are crucial for ubiquitination and trafficking to the yeast vacuole. In the mutants there was no simple correlation between phosphorylation and ubiquitination levels, suggesting that the two events may not be coupled.
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