Research

The highly conserved mitogen activated protein kinase (MAPK) signaling pathways are key players in the transduction of signals from the cell surface to the nucleus in response to environmental alterations. The canonical MAPK module comprises three components, MAPK kinase kinase (MAPKKK), MAPK kinase (MAPKK), and MAP kinase (MAPK), which are regulated by sequential phosphorylation events. Once activated, the MAPK phosphorylates a wide variety of cytoplasmic substrates including MAPK-activated protein kinases and RNA-binding proteins, or shifts into the nucleus to phosphorylate cell cycle regulatory proteins as well as specific transcription factors to execute a transcriptional program triggered by the stimuli.

General MAPKs Pathway

Our research group use as experimental model for this type of studies the fission yeast Schizosaccharomyces pombe, which is an organism not harmful and easy to grow. Strong experimental evidence confirms significant functional homology between the MAPK cascades of the S. pombe and those of higher cells, thus making this rod-shaped yeast an excellent model organism to unveil novel mechanisms of general significance linked to MAPK activation and downstream signaling. 

In contrast to mammalian cells, S. pombe has only three MAPK pathways known as the pheromone signaling pathway, the stress-activated protein kinase pathway (SAPK), and the cell integrity MAPK pathway (CIP), which is homologous to the ERK1/2 pathway, and has been our main research issue during the last years. The key component of this signaling cascade, MAP kinase Pmk1/Spm1, regulates in S. pombe multiple processes like cell wall construction and maintenance during stress, vacuole fusion, cytokinesis, morphogenesis, m-RNA stabilization, respiratory growth, and ionic homeostasis. The MAPK module also includes MAPKKK Mkh1 and MAPKK Pek1/Skh1, whose absence induces distinct phenotypes like altered cytokinesis, vacuole fusion defects, and increased growth sensitivity to saline ions or cell wall damaging agents. 

Notably, our recent observations suggest that the CIP-mediated response to environmental stresses is exposed to multiple regulatory layers through its interaction with different major signaling pathways, including: (i) TOR, that participates in cellular adaptation to altered nutritional and environmental conditions; (ii) phosphoinositide metabolism components that regulate morphogenesis and cell division; and (iii) elements of the cysteine-methylation and palmitoylation machinery, that elicit proper Rho GTPase membrane targeting and biological activity.