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Constitutive Activation of the Fission Yeast Pheromone-Responsive Pathway Induces Ectopic Meiosis and Reveals Ste11 as a Mitogen-Activated Protein Kinase Target

Søren Kjærulff, Inger Lautrup-Larsen, Søren Truelsen, Morten Pedersen, and Olaf Nielsen^*

Institute of Molecular Biology, University of Copenhagen, Copenhagen, Denmark

Received 5 July 2004/ Returned for modification 10 August 2004/ Accepted 29 November 2004

In the fission yeast Schizosaccharomyces pombe, meiosis normally takes place in diploid zygotes resulting from conjugation of haploid cells. In the present study, we report that the expression of a constitutively activated version of the pheromone-responsive mitogen-activated protein kinase kinase kinase (MAP3K) Byr2 can induce ectopic meiosis directly in haploid cells. We find that the Ste11 transcription factor becomes constitutively expressed in these cells and that the expression of pheromone-responsive genes no longer depends on nitrogen starvation. Epistasis analysis revealed that these conditions bypassed the requirement for the meiotic activator Mei3. Since Mei3 is normally needed for inactivation of the meiosis-repressing protein kinase Pat1, this finding suggests that the strong Byr2 signal causes inactivation of Pat1 by an alternative mechanism. Consistent with this possibility, we found that haploid meiosis was dramatically reduced when Ste11 was mutated to mimic phosphorylation by Pat1. The mutation of two putative MAPK sites in Ste11 also dramatically reduced the level of haploid meiosis, suggesting that Ste11 is a direct target of Spk1. Supporting this, we show that Spk1 can interact physically with Ste11 and also phosphorylate the transcription factor in vitro. Finally, we demonstrate that ste11 is required for pheromone-induced G₁ arrest. Interestingly, when we mutated Ste11 in the sites for Pat1 and Spk1 phosphorylation simultaneously, the cells could still arrest in G₁ in response to pheromone, suggesting the existence of yet a third bifurcation of the signaling pathway.

Present address: Novo Nordisk A/S, 2880 Bagsværd, Denmark.

Present address: Alpharma ApS, 2300 Copenhagen S, Denmark.

This article has been cited by other articles:

• Kjaerulff, S., Andersen, N. R., Borup, M. T., Nielsen, O. (2007). Cdk phosphorylation of the Ste11 transcription factor constrains differentiation-specific transcription to G1. Genes Dev. 21: 347-359 [Abstract] [Full Text]  
• Mata, J., Bahler, J. (2006). Global roles of Ste11p, cell type, and pheromone in the control of gene expression during early sexual differentiation in fission yeast. Proc. Natl. Acad. Sci. USA 103: 15517-15522 [Abstract] [Full Text]