The Yak1 Protein Kinase Lies at the Center of a Regulatory Cascade Affecting Adhesive Growth and Stress Resistance inSaccharomyces cerevisiae

Abstract

In Saccharomyces cerevisiae, adhesive growth on solid surfaces is mediated by the flocculin Flo11 to confer biofilm and filament formation. Expression of FLO11 is governed by a complex regulatory network that includes, e.g., the protein kinase A (PKA) signaling pathway. In addition, numerous regulatory genes, which have not been integrated into regulatory networks, affect adhesive growth, including WHI3 encoding an RNA-binding protein and YAK1 coding for a dual-specificity tyrosine-regulated protein kinase. In this study, we present evidence that Whi3 and Yak1 form part of a signaling pathway that regulates FLO11-mediated surface adhesion and is involved in stress resistance. Our study further suggests that Whi3 controls YAK1 expression at the post-transcriptional level and that Yak1 targets the transcriptional regulators Sok2 and Phd1 to control FLO11. We also discovered that Yak1 regulates acidic stress resistance and adhesion via the transcription factor Haa1. Finally, we provide evidence that the catalytic PKA subunit Tpk1 inhibits Yak1 by targeting specific serine residues to suppress FLO11. In summary, our data suggest that Yak1 is at the center of a regulatory cascade for adhesive growth and stress resistance, which is under dual control of Whi3 and the PKA subunit Tpk1.

The RNA-Binding Protein Whi3 Is a Key Regulator of Developmental Signaling and Ploidy inSaccharomyces cerevisiae

“…We have previously shown that Whi3 is able to control biofilm development by both post-transcriptional control of Yak1 and yet unknown, Yak1-independent mechanisms (Malcher et al 2011). We therefore wanted to know whether Whi3 is able to control additional yeast developmental regulators at the post-transcriptional level.…”

“…The RNA recognition motif (RRM) protein Whi3 is another RNA-binding protein that controls S. cerevisiae adhesion and biofilm formation. In contrast to Mpt5, Whi3 activates these processes and targets the dual-specificity tyrosine-regulated protein kinase Yak1 (Mösch and Fink 1997;Malcher et al 2011). Specifically, Whi3 controls production of Yak1 at the post-transcriptional level, which in turn activates expression of FLO11, a cell surface flocculin for adhesion and biofilm formation, via the transcription factors Sok2 and Phd1 (Gimeno and Fink 1994;Ward et al 1995;Lo and Dranginis 1998;Guo et al 2000;Pan and Heitman 2000;Reynolds and Fink 2001;Malcher et al 2011).…”

“…Yak1-dependent functions of Whi3 further include control of stress responses via the transcription factors Msn2 and Msn4 (Lee et al 2008) and acidic stress resistance mediated by the transcriptional regulator Haa1 (Fernandes et al 2005;Malcher et al 2011). However, Whi3 also seems to control filamentation and biofilm formation by yet unknown Yak1-independent mechanisms (Malcher et al 2011), which might include other components of the complex signaling network that controls FLO11 (Brückner and Mösch 2012).…”

“…The functionality of signal transduction pathways crucially depends on the timely availability of individual components at sufficient levels to ensure adequate signaling capacity. A number of studies in different eukaryotes have shown that the production of individual signaling proteins is under the control not only of transcriptional regulators, but also of RNA-binding proteins (Lasko 2003;Sugiura et al 2003;Prinz et al 2007;Stewart et al 2007;Malcher et al 2011). This suggests that RNA-binding proteins could regulate the performance of whole signaling networks, but a precise view of key interconnections is often lacking.…”

“…Specifically, Whi3 controls production of Yak1 at the post-transcriptional level, which in turn activates expression of FLO11, a cell surface flocculin for adhesion and biofilm formation, via the transcription factors Sok2 and Phd1 (Gimeno and Fink 1994;Ward et al 1995;Lo and Dranginis 1998;Guo et al 2000;Pan and Heitman 2000;Reynolds and Fink 2001;Malcher et al 2011). Yak1-dependent functions of Whi3 further include control of stress responses via the transcription factors Msn2 and Msn4 (Lee et al 2008) and acidic stress resistance mediated by the transcriptional regulator Haa1 (Fernandes et al 2005;Malcher et al 2011). However, Whi3 also seems to control filamentation and biofilm formation by yet unknown Yak1-independent mechanisms (Malcher et al 2011), which might include other components of the complex signaling network that controls FLO11 (Brückner and Mösch 2012).…”