Ras2 signals via the Cdc42/Ste20/mitogen-activated protein kinase module to induce filamentous growth in Saccharomyces cerevisiae.

Abstract

RAS2val19, a dominant activated form of Saccharomyces cerevisiae Ras2, stimulates both filamentous growth and expression of a transcriptional reporter FG(TyA)::lacZ but does not induce the mating pathway reporter FUS1::lacZ. This induction depends upon elements of the conserved mitogen-activated protein kinase (MAPK) pathway that is required for both filamentous growth and mating, two distinct morphogenetic events. Full induction requires Ste20 (homolog of mammalian p65PAK protein kinases), Ste11 [an MEK kinase (MEKK) or MAPK kinase (MEK) kinase], Ste7 (MEK or MAPK kinase), and the transcription factor Ste12. Moreover, the Rho family protein Cdc42, a conserved morphogenetic G protein, is also a potent regulator of filamentous growth and FG(TyA)::lacZ expression in S. cerevisiae. Stimulation of both filamentous growth and FG(TyA)::lacZ by Cdc42 depends upon Ste20. In addition, dominant negative CDC42Ala118 blocks RAS2val19 activation, placing Cdc42 downstream of Ras2. Our results suggest that filamentous growth in budding yeast is regulated by an evolutionarily conserved signaling pathway that controls cell morphology.

The control of morphogenesis in Saccharomyces cerevisiae by Elm1 kinase is responsive to RAS/cAMP pathway activity and tryptophan availability

“…This activity has been implicated in filamentous growth control: lowering cAMP levels in RAS2 val19 cells through the overexpression of the phosphodiesterase Pde2, which hydrolyses cAMP, suppresses the induction of pseudohyphal growth by activated Ras2 (Ward et al, 1995), suggesting that the RAS/cAMP pathway is involved in filamentous growth. However, the RAS-dependent induction of filamentous growth has also been shown to be dependent on a different signalling pathway: the conserved STE/mitogen-activated protein (MAP) kinase pathway (Mosch et al, 1996). Therefore, it appears that Ras2 plays a complex role in the development of yeast cell shape and is involved in multiple signalling pathways that control morphogenesis.…”

Two novel targets of the MAP kinase Kss1 are negative regulators of invasive growth in the yeast Saccharomyces cerevisiae.

“…Because Stel2 acts at the promoters of genes required for both mating pheromone response and for invasive growth, yet Digl and Dig2 binding to Stel2 affects the action of this transcriptional regulator only at the latter class of promoters, it is likely that this differential effect of Digl and Dig2 reflects some intrinsic difference between how Stel2 acts at these two different classes of promoters (Laloux et al 1994;M6sch et al 1996). Indeed, another transcriptional regulator, Tecl (Gavrias et al 1996), that is required for invasive growth and that acts in cooperation with Stel2 (H. Madhani and G.R.…”

Differential regulation of cell wall biogenesis during growth and development in yeast

“…A MAP kinase pathway (the filamentous growth pathway) sharing components with the mating MAP kinase cascade is crucial (reviewed by Gustin et al, 1998 ;Banuett, 1998), but another input is through a G-protein to Ras2p, relaying a signal via PKA (Kubler et al, 1997 ;Lorenz & Heitman, 1997 ;Pan & Heitman, 1999 ;Robertson & Fink, 1998). These pathways are interconnected, since, for example, Ras2p can activate the filamentous growth MAP kinase cascade (Mosch et al, 1996), but they also have separate outputs, as signalling through PKA does not require the MAP kinase (Pan & Heitman, 1999).…”