Inhibitory and activating functions for MAPK Kss1 in the S. cerevisiae filamentous- growth signalling pathway

Abstract

Mitogen-activated protein kinase (MAPK) cascades are conserved signalling modules that regulate responses to diverse extracellular stimuli, developmental cues and environmental stresses. A MAPK is phosphorylated and activated by a MAPK kinase (MAPKK), which is activated by an upstream protein kinase, such as Raf, Mos or a MAPKK kinase. Ste7, a MAPKK in the yeast Saccharomyces cerevisiae, is required for two developmental pathways: mating and invasive (filamentous) growth. Kss1 and Fus3, the MAPK targets of Ste7, are required for mating, but their role in invasive growth has been unclear. Because no other S. cerevisiae MAPK has been shown to function in invasive growth, it was proposed that Ste7 may have non-MAPK targets. We show instead that Kss1 is the principal target of Ste7 in the invasive-growth response in both haploids and diploids. We demonstrate further that Kss1 in its inactive form is a potent negative regulator of invasive growth. Ste7 acts to relieve this negative regulation by switching Kss1 from an inhibitor to an activator. These results indicate that this MAPK has a physiologically important function in its unactivated state. Comparison of normal and MAPK-deficient cells indicates that nitrogen starvation and activated Ras stimulate filamentous growth through both MAPK-independent and MAPK-dependent means.

A walk-through of the yeast mating pheromone response pathway

“…The MAPKs, particularly Kss1, also regulate Ste12 by a novel mechanism: repression of transcription by unactivated MAP kinase [10,11,30,97]. Unphosphorylated Kss1 binds directly to Ste12, and potently represses Ste12-driven transcription [10].…”

“…The Dig1 and Dig2 proteins are required cofactors in Kss1-imposed repression of Ste12 [11]; Kss1, by virtue of its ability to bind to both Ste12 and Dig1/2, may help anchor the latter to the former. Fus3 binds much less strongly to Ste12 than Kss1 does [10], and is a correspondingly weaker repressor [30]. Phosphorylation of Kss1 by Ste7 weakens Kss1-Ste12 binding and consequently relieves Kss1-imposed repression, simultaneously activating Kss1 catalytic activity [10].…”

Stress induces depletion of Cdc25p and decreases the cAMP producing capability in Saccharomyces cerevisiae

“…However, it cannot be excluded that Cdc25p, activator of Ras proteins, also controls another Ras-dependent pathway. Supporting this hypothesis, several reports have shown an involvement of Ras in the control of the MAP kinase pathway leading to invasive growth (Cherkasova et al, 2003;Cook et al, 1997). This pathway could converge with the cAMP-PKA pathway upon Msn2p and Msn4p, which are also involved in the control of invasive and filamentous growth (Ho & Bretscher, 2001).…”

Inhibition of Cdc42-dependent signalling in Saccharomyces cerevisiae by phosphatase-dead SigD/SopB from Salmonella typhimurium

“…6b). The signal transduction pathway in which Kss1 participates is mediated by Cdc42 and is related to pseudofilamentation (Zhou et al, 1993;Cook et al, 1997;Lee & Elion, 1999). The expression of a mutant version of SigD bearing an internal deletion in the non-catalytic region (GST-SigD D118-142 ), which retains some phosphatase activity but is unable to disrupt actin function either in yeast or in mammalian cells (Alemán et al, 2005), did not lower Kss1 phosphorylation levels (Fig.…”