Specificity of MAP kinase signaling in yeast differentiation.
Lee Bardwell, Walid Sabbagh, Laura Flatauer
Developmental &
Cell Biology, Univ. of California, Irvine, 5207 McGaugh Hall, Irvine, CA
92697-2300, USA
Often, the transmission of different upstream signals
involves common components, yet elicits distinct (and appropriate)
outcomes. How specificity from signal to cellular response is maintained
in such cases is not well understood. In haploid cells of the yeast
S. cerevisiae, two distinct developmental options - mating and
filamentous invasive growth - are both regulated by the same mitogen-activated protein kinase (MAPK) cascade, containing the MAPK kinase Ste7
and its target MAPKs Kss1 and Fus3. Despite this overlap, exposure of
cells to mating pheromone does not result in the hyperactivation of
filamentation genes. Our recent studies indicate that signal identity in
this system is encoded in the magnitude and duration of MAPK activation,
and not by competition for pathway-specific components. Hence, the yeast
model bears a much closer resemblance to the paradigm of proliferation
vs. differentiation in mammalian cells, as exemplified by the PC12
system, than was previously appreciated. MAPK activation during mating
is transient because one of the MAPKs (Fus3) initiates a negative
feedback circuit that downregulates the phosphorylation of both MAPKs.
Our latest findings regarding the molecular mechanism of this feedback
will be presented.
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