3PK, A NEW MITOGEN-ACTIVATED PROTEIN KINASE-ACTIVATED PROTEIN-KINASE LOCATED IN THE SMALL-CELL LUNG-CANCER TUMOR-SUPPRESSOR GENE REGION

NotI linking clones, localized to the human chromosome 3p21.3 region a nd homozygously deleted in small cell lung cancer cell lines NCI-H740 and NCI-H1450, were used to search for a putative tumor suppressor gen e(s). One of these clones, NL1G210, detected a 2.5-kb mRNA in all exam ined human tissues, expression being especially high in the heart and skeletal muscle. Two overlapping cDNA clones containing the entire ope n reading frame were isolated from a human heart cDNA library and full y characterized. Computer analysis and a search of the GenBank databas e revealed high sequence identity of the product of this gene to serin e-threonine kinases, especially to mitogen-activated protein kinase-ac tivated protein kinase 2, a recently described substrate of mitogen-ac tivated kinases. Sequence identity was 72% at the nucleotide level and 75% at the amino acid level, strongly suggesting that this protein is a serine-threonine kinase. Here we demonstrate that the new gene, ref erred to as 3pK (for chromosome 3p kinase), in fact encodes a mitogen activated protein kinase-regulated protein serine-threonine kinase wit h a novel substrate specificity.