Regulació de la via de senyalització MEK5/ERK5 i el seu paper en l'expressió gènica

Cells respond to extracellular stimuli trough the activation of different transduction pathways. MAP kinases are a family of enzymes activated in response to different sort of stimulus. ERK5 is one of the lasts members of the MAP kinase family identified. As the other members of this family, ERK5 is activated by dual phosphorylation on Thr and Tyr residues. MEK5 has been characterised as the only kinase capable of activating ERK5, and is unable to activate other MAP kinases. ERK5 respond to several extracellular stimuli (growth factors, oxidative stress, etc) and has been implicated in the control of cell proliferation. Some of the ERK5 substrates identified are transcription factors, what suggests that may be involved in the regulation of several genes. It has been also described that the C-terminal domain of ERK5 can act as a regulator of gene expression. In view of that, the main goal of this project is to identify using cDNA microarrays some of the genes regulated by the specific activation of EERK5 ant to study the regulation of some of them. The regulation of ERK5 by ras seems to be dependent on cell type. In PC12 cells has been described that ras activates ERK5. In this cells NGF and EGF activate ERK5 with a kinetics similar to ERK1/2. Thus, where as EGF induces a transient activation of ERK1/2, the response to NGF is a sustained activation of ERK1/2. In the case of ERK1/2 the initial activation by NGF requires ras, but its activation is sustained by rap1. Thus, we propose to study the role of rap1 on ERK5 activation in PC12 cells.