IDENTIFICATION AND SEQUENCE OF HUMAN PKY, A PUTATIVE KINASE WITH INCREASED EXPRESSION IN MULTIDRUG-RESISTANT CELLS, WITH HOMOLOGY TO YEAST PROTEIN-KINASE YAK1

We have previously shown that several protein kinases are present in h igher activity levels in multidrug resistant cell lines, such as KB-V1 . We have now isolated a gene that codes for a putative protein kinase , PKY, of over 130 kDa that is expressed at higher levels in multidrug -resistant cells. RNA from KB-V1 multidrug-resistant cells was reverse -transcribed and amplified by using primers derived from consensus reg ions of serine-threonine kinases and amplified fragments were used to recover overlapping clones from a KB-V1 cDNA library. An open reading frame of 3648 bp of DNA sequence predicting 1215 aa, has been identifi ed. This cDNA hybridizes to a mRNA of about 7 kb which is expressed at high levels in human heart and muscle tissue and overexpressed in dru g-resistant KB-V1 and HL60/ADR cells. Because its closest homolog is t he yeast serine/threonine kinase, Yak1, we have called this gene PKY. PKY is also related to the protein kinase family that includes Cdks, G sk-3, and MAPK proline-directed protein kinases. This protein represen ts the first of its type known in mammals and may be involved in growt h control pathways similar to those described for Yak1, as well as pos sibly playing a role in multidrug resistance. (C) 1997 Elsevier Scienc e B.V.