Molecular cloning of a novel human protein kinase, kpm, that is homologous to warts/lats, a Drosophila tumor suppressor.

Abstract

A novel human protein kinase, designated kpm, was identified and molecularly cloned. The isolated cDNA clone had an open reading frame consisting of 1088 amino acid residues with a putative kinase domain located near the carboxy-terminus. Homology search revealed that kpm belongs to a subfamily of serine/threonine protein kinases including warts/lats, a Drosophila tumor suppressor. Among these, kpm is most homologous to, but distinct from, recently reported LATS1, a human homolog of Drosophila warts/lats. Northern blot analysis disclosed that kpm is expressed as a 6.0 kb transcript in most of the tissues examined and also as an additional shorter 4.0 kb transcript in testis. Western blotting using polyclonal rabbit anti-kpm antibody detected kpm protein as a band with an apparent Mr of 150 kD. Immune complex kinase assay of HA-tagged kpm showed that kpm had kinase activity and phosphorylated itself in vitro. Studies with synchronized HeLa cells indicated that kpm protein was expressed relatively constantly throughout the cell cycle and underwent significant phosphorylation at mitotic phase. These results suggest that kpm plays a role in cell cycle progression during mitosis and its deletion or dysfunction might be involved in certain types of human cancers.