Environmental
perturbations often provoke a transient depolarization of the actin
cytoskeleton, during which bud construction is delayed while cells
adapt to the insult. In these cells, the morphogenesis checkpoint
stabilizes the Swe1p kinase, which accumulates and inhibits Cdc28p,
halting the cell cycle in G2 until the actin can repolarize and
complete bud construction. Many signaling pathways involve kinase
cascades culminating in activation of MAPKs (of which there are 5 in
yeast). The Pkc1p/Mpk1p MAPK pathway was specifically required to
generate an effective morphogenesis checkpoint response, and actin
depolymerization caused a dramatic induction of Mpk1p
phosphorylation. Thus, Mpk1p is activated upon actin perturbation and
is essential for an effective checkpoint response to such
perturbation. The Mpk1p pathway is thought to respond to cell
wall/plasma membrane defects through putative plasma membrane sensors
(Wsc1p, Mid2p), which activate exchange factors (Rom2p, Rom2p),
promoting GTP-loading of Rho1p, which is an activator of Pkc1p.
Surprisingly, these pathways were not required for checkpoint
function. Stabilization of Swe1p did not compensate for the loss of
Mpk1p. However, elimination of Mih1p (the phosphatase that
counteracts Swe1p action) suppressed the checkpoint defect of cells
lacking Mpk1p. This suggests that the Pkc1p-Mpk1p cascade promotes
Mih1p inhibition during a checkpoint response.
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