ERK2 CD domain mutation from a human cancer cell line enhanced anchorage-independent cell growth and abnormality in Drosophila.
In a human cancer cell line, we previously found a mutation in codon 322 of the extracellular signal-regulated kinase (ERK2E322K), the protein showed a faster migration when compared to wild-type in SDS-PAGE and constitutive phosphorylation. However, the reason for the faster migration, and the biochemical and biological properties of the mutation is unknown. In this study, we report that the amino acid charge-change mutation in the common docking (CD) domain is important for fast migration. In vitro binding of ERK2E322K to MKP1 and RSK2 was lost, resulting in constitutive activation and possibly contributing to a more efficient colony formation in soft agar. We established transgenic flies by carrying the corresponding CD domain mutation, DERKE335K, which developed smaller and rougher eyes compared with the wild-type. Taken together, these data are consistent with ERK2E322K loss of contact with downstream effectors and its constitutive activation, presenting an oncogenic potential and weak abnormality in differentiation.
Mahalingam
Marthandan
M
Department of Molecular Cellular Oncology and Microbiology, Tokyo Medical and Dental University, Tokyo, Japan.
Arvind
Ramanathan
R
Ida
Hiroyuki
H
Murugan
Avaniyapuram Kannan
AK
Yamaguchi
Masamitsu
M
Tsuchida
Nobuo
N
D000818:Animals; D030801:Animals, Genetically Modified; D041702:BALB 3T3 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004330:Drosophila; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D005124:Eye Abnormalities / Q000235:genetics*; D006801:Humans; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry / Q000235:genetics*; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism
D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; D019950:Mitogen-Activated Protein Kinase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1