In deletion mutant analyses of potential phosphorylation sites in RLIP76, we identified T
297 and S
509 as targets for phosphorylation by PKCα. Phosphorylation at T
297 increased doxorubicin (DOX)-transport activity
![not, vert, similar](http://www.sciencedirect.com/scidirimg/entities/223c.gif)
2-fold for RLIP76 purified from recombinant source, or from three small (H69, H1417, H1618) and three non-small cell, one each derived from H226 (squamous), H358 (bronchio alveolar), and H1395 (adenocarcinoma) lung cancer cell lines. T
297 phosphorylation conferred sensitivity to tryptic digestion at R
293. The specific activity for DOX-transport by RLIP76 purified from non-small cell, which was primarily in the phosphorylated form, was approximately twice that in small cell lung cancer cell lines. These finding offer a novel explanation for the observed intrinsic differences in sensitivity to DOX between non-small cell and small cell lung cancer cell lines.