The MAP kinase (mitogen-activated protein kinase) family has been implicated in a variety of signalling pathways. Stimuli which activate these kinases can eventually cause differentiation, proliferation, or an alteration in the cellular status. MAP kinases are interesting because they can translocate from the cytoplasm to the nucleus. This suggests that they may be the proteins which activate the transcription factors responsible for the primary response of the cell. Although this correlative evidence is interesting, an actual biological role for MAP kinase in vivo, has not been firmly established yet. Transient expression of dominant inhibitory mutants of MAP kinase cause growth arrest in 3T3 cells and can revert transformation induced by oncogenes such as v-raf, Dbl, and Vav. This indicates that MAP kinase may have a role in the transformation of cells. The question remains though, as to how MAP kinase functions in transformation and is MAP kinase alone sufficient to transform cells or are other parallel signals required. To address these questions, constitutively active and dominant inhibitory mutants of MAP kinase will be generated. These mutants will be introduced into cells and the regulation of a number of transcription factors and immediate-early genes will be analyzed.
| Murphy, Leon O; Smith, Sallie; Chen, Rey-Huei et al. (2002) Molecular interpretation of ERK signal duration by immediate early gene products. Nat Cell Biol 4:556-64 |
