PRK, A CYTOKINE-INDUCIBLE HUMAN PROTEIN SERINE THREONINE KINASE WHOSEEXPRESSION APPEARS TO BE DOWN-REGULATED IN LUNG CARCINOMAS/

We have cloned and characterized a putative protein serine/threonine k inase termed prk through a combination of polymerase chain reaction an d conventional cDNA library screening approaches. There are apparently two distinct domains within pll protein deduced from its nucleotide s equences. 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 muri ne 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 restric ted to a very limited number of tissues with placenta, ovaries, and lu ng containing detectable amounts of prk mRNA. prk mRNA expression is a lso detected at a low level in the megakaryocytic cell line Dami, MO7e , and three brain glioma cell lines, In addition, refeeding of serum-d eprived MO7e, Dami, and K562 cells of hematopoietic origin and GMOO637 D of lung fibroblasts rapidly activates prk, mRNA expression with its peak induction around 2 h after serum addition, pl-fi gene activation by the serum requires no new protein synthesis, The recombinant cytoki nes such as interleukin-3 and thrombopoietin also activate prk mRNA ex pression in MO7e cells, Furthermore, a survey of RNAs isolated from th e tumor and the uninvolved tissues from 18 lung cancer patients reveal s that prk mRNA expression is significantly down-regulated in tumor ti ssues, Southern blotting analysis indicates that the pl h gene is pres ent in a single copy in the genome of tumors and normal cells, Taken t ogether, these results suggest that prk expression may be restricted t o proliferating cells and involved in the regulation of cell cycle pro gression, The molecular cloning- of prk cDNA will facilitate the study of its biological role as well as its potential role in tumorigenesis .