Signalling through the atypical MAP kinase ERK3 and ERK4
Protein kinases with its 518 members represent on of the largest family of enzymes encoded by the human genome. Signalling pathways controlled by protein kinases underlie a great number of human diseases and are involved in the initiation and progression all cancer forms. This has made kinases as a prioritized target for development of novel drugs especial in the area for cancer therapy. One of the major challenges for the utilizing the whole human kinome as target for drugs are lack of knowledge into the function and targets for a majority of the human kinases.
The protein kinases ERK3 and ERK4 are atypical members of the mitogen-activated protein kinase (MAPK) family. They exhibits striking differences when compared with all other MAP kinase isoforms, most notably in the substitution of the T-E-Y motif within the activation loop of the kinase by the sequence SEG and in the presence of an unique C-terminal extension. Although ERK3 and ERK4 were amongst the first MAP kinases to be identified there are still little information available into their function and regulation. We have recently identified MAPKAP kinase 5 (MK5) as the first downstream target for ERK3 and ERK4.
This project aims to decipher the signalling pathway defined by the atypical MAP kinases ERK3 and ERK4. This will include studies aimed at dissecting the biochemical mechanisms, which underlie the regulation of ERK3 and ERK4 activities as well as studies aimed towards definition of the physiological roles of these kinases in health and disease.