Three major signal transduction pathways that control the sexual
development in fission yeast Schizosaccharomyces pombe have been studied.
One of the pathway transmit the pheromonal signal through the RAS-MAP kinase
pathway, the other two pathways transmit the signals of starvation through
the cAMP pathway and the stress regulatory pathway. Among these three signal
transduction pathways, the Ras signal transduction pathway play a major
The RAS proteins are highly conserved GTP binding proteins in all eukaryotic organisms. In contrast to many components of the RAS-cAMP pathway have been characterized in Saccharomyces cerevisiae, a few components have been characterized in S. pombe. The role of Ras in the signal transduction pathway of the S. pombe is different from S. cerevisiae. RAS in S. pombe is not essential for the growth and control the downstream MAP kinase cascade as in higher eukaryotes, whereas RAS controls adenylyl cyclase in S.cerevisiae. We looked for the novel factors which interact with RAS in fission yeast and isolated mutants that suppress the function of ras deficient diploid strains. From the screening, two mutants called sam3 and sam9 are isolated as the ones that bypass loss of the fucntion of ras. From the sam3 dominant mutant, we isolated the sla1 gene, a homolog of La from human.
The cAMP pathway in fission yeast
An adenylyl cyclase associated protein called CAP was identified
as a candidate that connect RAS and adenylyl cylcase in S.cerevisiae.
Genetic studies show CAP to be a multi-functional molecule with three distinct
domains. The N-terminal portion of CAP is required for the full responsiveness
of RAS to adenylyl cyclase, whereas the C-terminal portion is involved
in the cytoskeltal organization and nutritional signaling in S.cerevisiae.
The third domain in the central region is not well understood. To understand
CAP functions in S. pombe more precisely, We looked for the interacting
protein with CAP. Using two-hybrid screening, we isolated the CAP interacting
protein called Csh3. Csh3 has the SH3 domain in the middle region and serve
the binding site for CAP. The interaction of Csh3 and CAP will give us
the clue how the signal transduction pathway is connected with the protein
localization of CAP.
To explore the signal transduction pathway in fission yeast will give us the general idea of not only the mechanism of cell differentiation in fission yeast, but will also the function of human ras oncogene and finally cancer.