Abstract:
: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.
journal_name
Oncol Repjournal_title
Oncology reportsauthors
Mahalingam M,Arvind R,Ida H,Murugan AK,Yamaguchi M,Tsuchida Nsubject
Has Abstractpub_date
2008-10-01 00:00:00pages
957-62issue
4eissn
1021-335Xissn
1791-2431journal_volume
20pub_type
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