Cloning and characterization of Krct, a member of a novel subfamily of serine/threonine kinases.
Protein kinases frequently play key roles in the normal regulation of growth and development in eukaryotic organisms. As a consequence, aberrant expression or mutations in this family of molecules frequently result in transformation. Previously, we have conducted a screen to identify protein kinases that are expressed in the mouse during mammary gland development and in breast cancer cell lines. We now describe the molecular cloning, characterization and expression of Krct, a novel serine/threonine protein kinase unrelated to previously defined families of protein kinases. At the mRNA level, Krct is widely expressed throughout murine development and in adult tissues. Despite its ubiquitous expression, Krct is expressed preferentially within specific cellular compartments in multiple tissues, in particular within the testis and gastrointestinal tract. At the amino acid level, Krct is most closely related to four previously undescribed kinases in Saccharomyces cerevisiae, Arabidopsis thaliana and Caenorhabditis elegans. Together, these kinases appear to define a novel subfamily of serine/threonine protein kinases. Krct possesses an unusually long 5'-untranslated region containing multiple upstream initiation codons and, in this regard, is similar to many proto-oncogenes that regulate normal growth and differentiation. In addition, Krct is located on mouse chromosome 11 closely linked to the epidermal growth factor receptor and, therefore, is likely to be co-amplified in a variety of human tumors.
Stairs
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DB
Department of Molecular and Cellular Engineering and Division of Endocrinology, Diabetes and Metabolism, Stellar-Chance Laboratories, Room 309A, University of Pennsylvania School of Medicine, 422 Curie Boulevard, Philadelphia, PA 19104-6100, USA.
Perry Gardner
H
H
Ha
S I
SI
Copeland
N G
NG
Gilbert
D J
DJ
Jenkins
N A
NA
Chodosh
L A
LA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009115:Muridae; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D012333:RNA, Messenger; D014157:Transcription Factors; C486000:Stk16 protein, mouse; D017346:Protein Serine-Threonine Kinases