Open Access3pK, a New Mitogen-Activated Protein Kinase-Activated Protein Kinase Located in the Small Cell Lung Cancer Tumor Suppressor Gene Region
Author(s) -
Gunamani Sithanandam,
Farida Latif,
Fuh Mei Duh,
Ricardo A. Bernal,
U Smola,
H Li,
Igor Kuzmin,
Viktor Wixler,
L. Geil,
Safal Shrestha
Publication year - 1996
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.16.3.868
Subject(s) - biology , c raf , map2k7 , cyclin dependent kinase 4 , protein kinase a , akt3 , cyclin dependent kinase 2 , microbiology and biotechnology , mitogen activated protein kinase kinase , map kinase kinase kinase , kinase , biochemistry , threonine , serine , phosphorylation
NotI linking clones, localized to the human chromosome 3p21.3 region and homozygously deleted in small cell lung cancer cell lines NCI-H740 and NCI-H1450, were used to search for a putative tumor suppressor gene(s). One of these clones, NL1G210, detected a 2.5-kb mRNA in all examined human tissues, expression being especially high in the heart and skeletal muscle. Two overlapping cDNA clones containing the entire open reading frame were isolated from a human heart cDNA library and fully characterized. Computer analysis and a search of the GenBank database to reveal high sequence identity of the product of this gene to serine-threonine kinases, especially to mitogen-activated protein kinase-activated protein kinase 2, a recently described substrate of mitogen-activated kinases. Sequence identitiy 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, referred to as 3pK (for chromosome 3p kinase), in fact encodes a mitogen-activated protein kinase-regulated protein serine-threonine kinase with a novel substrate specificity.