prk, a Cytokine-inducible Human Protein Serine/Threonine Kinase Whose Expression Appears to be Down-regulated in Lung Carcinomas*

Abstract

We have cloned and characterized a putative protein serine/threonine kinase termed prk through a combination of polymerase chain reaction and conventional cDNA library screening approaches. There are apparently two distinct domains within prk protein deduced from its nucleotide sequences. The amino-terminal portion has the feature of the catalytic domain of a serine/threonine kinase and shows strong homology to mouse fnk and other polo family kinases including mouse snk, human and murine plk, Drosophila polo, and yeast Cdc5. The carboxyl-terminal portion, presumably the regulatory domain, shares extensive homology to mouse fnk. Northern blotting analyses reveal that prk expression is restricted to a very limited number of tissues with placenta, ovaries, and lung containing detectable amounts of prk mRNA. prk mRNA expression is also detected at a low level in the megakaryocytic cell line Dami, MO7e, and three brain glioma cell lines. In addition, refeeding of serum-deprived MO7e, Dami, and K562 cells of hematopoietic origin and GMOO637D of lung fibroblasts rapidly activates prk mRNA expression with its peak induction around 2 h after serum addition. prk gene activation by the serum requires no new protein synthesis. The recombinant cytokines such as interleukin-3 and thrombopoietin also activate prk mRNA expression in MO7e cells. Furthermore, a survey of RNAs isolated from the tumor and the uninvolved tissues from 18 lung cancer patients reveals that prk mRNA expression is significantly down-regulated in tumor tissues. Southern blotting analysis indicates that the prk gene is present in a single copy in the genome of tumors and normal cells. Taken together, these results suggest that prk expression may be restricted to proliferating cells and involved in the regulation of cell cycle progression. The molecular cloning of prk cDNA will facilitate the study of its biological role as well as its potential role in tumorigenesis.