In human and zebrafish tumors the ERK signalling pathway, which is essential for vertebrate development, is frequently deregulated. Previously, the researchers demonstrated that ERK2 is crucial for cell migration and early zebrafish embryogenesis. In this new study they looked further into the ERK2 function. The researchers generated constitutively active mutant forms of the ERK proteins by introducing conserved point mutations. They validated the enhanced protein activity in vitro by transfection of constructs into zebrafish fibroblast (zf4) cells and established elevated phosphorylation levels of downstream targets P90RSK and CREB. Using the PamGene platform for kinase activity profiling new targets were identified in embryos injected with FGF8 or ERK2 mRNAs. The researchers detected both FGF8 specific and common signalling targets. Interestingly, with both mRNAs they found increased phosphorylation levels of CDK1, which is critical for proper G2/M phase transition and mitotic entry in proliferation control. These results point out that constitutive activation of the ERK2 pathway leads to enhanced, possibly oncogenic, proliferation.
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Generation of constitutive active ERK mutants as tool for cancer research in zebrafish