The human cot proto-oncogene encodes two protein serine/threonine kinases with different transforming activities by alternative initiation of translation.
The cot gene is an oncogene encoding serine/threonine kinases isolated by DNA transfection assay. In this study, we isolated cDNA for the human cot protooncogene (proto-cot gene) and examined the structure and function of its gene products. The proto-cot gene has an open reading frame encoding 467 amino acids of which the first 397 amino acids are identical to those in the corresponding part of the cot gene. The protein products of the proto-cot gene were identified as 58- and 52-kDa proteins with intrinsic protein serine/threonine kinase activity. These two protein species were suggested to be generated by alternative initiation from two AUGs. The 58- and 52-kDa proteins are both localized predominantly in the cytosol, but the 58-kDa protein has a shorter half-life than the 52-kDa protein, suggesting the importance of the amino-terminal domain in regulating the stability of the proto-Cot protein. More interestingly, the 58-kDa protein showed stronger transforming activity than the 52-kDa protein, although this activity was much weaker than that of the Cot oncoprotein. Thus, the amino-terminal domain of the Cot protein may be necessary for cellular transformation, whereas the carboxyl-terminal domain may negatively regulate the transforming activity.
Aoki
M
M
Department of Oncogene Research, Osaka University, Japan.
Hamada
F
F
Sugimoto
T
T
Sumida
S
S
Akiyama
T
T
Toyoshima
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D016367:Baculoviridae / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D017931:DNA Primers; D018076:DNA, Complementary / Q000378:metabolism; D015870:Gene Expression; D015321:Gene Rearrangement; D006801:Humans; D020930:MAP Kinase Kinase Kinases; D008715:Methionine / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016366:Open Reading Frames; D010442:Peptide Chain Initiation, Translational; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D011519:Proto-Oncogenes; D013462:Sulfur Radioisotopes; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D018076:DNA, Complementary; C000715470:MAS1 protein, human; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D013462:Sulfur Radioisotopes; D008715:Methionine; D017346:Protein Serine-Threonine Kinases; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human