Possible integration of upstream signals at Cdc42 in filamentous differentiation of S. cerevisiae

Various environmental stimuli (such as nitrogen starvation, short‐chain alcohols and slowed DNA synthesis) induce filamentous differentiation in S. cerevisiae . Genetic mutations (such as deletion of the mitotic cyclin gene CLB2 ) cause constitutive filamentous differentiation. Although different stimulus‐induced filamentous differentiation involves different signalling pathways, Cdc42 has been identified as a common regulator. We show here that Cdc42 is also required for hydroxyurea (HU)‐induced and clb2 Δ‐caused filamentous growth. We show that the mitotic CDK Clb2/Cdc28 functions upstream of Cdc42 in regulating filamentous differentiation. This result points to possible existence of a Cdc42‐MAPK‐Clb2/Cdc28 positive feedback loop in the signalling of filamentous differentiation. We report isolation of a cdc42‐Y40F allele that blocks HU‐induced, but not nitrogen starvation‐induced, short‐chain alcohol‐induced or clb2 Δ‐caused, filamentation. Based on these results, we propose a model in which Cdc42 functions as a possible integrator for the upstream signals of filamentous differentiation (from the filamentous growth MAPK pathway, the cAMP pathway and the Mec1/Rad53 checkpoint pathway). We also show evidence that the mitotic CDK inhibitor Swe1 may mediate the cross‐talk between the cAMP and MAPK pathways. Copyright © 2005 John Wiley & Sons, Ltd.