A downstream target of RHO1 small GTP-binding protein is PKC1, a homolog of protein kinase C, which leads to activation of the MAP kinase cascade in Saccharomyces cerevisiae.

Abstract

The RHO1 gene in Saccharomyces cerevisiae encodes a homolog of the mammalian RhoA small GTP‐binding protein, which is implicated in various actin cytoskeleton‐dependent cell functions. In yeast, Rho1p is involved in bud formation. A yeast strain in which RHO1 is replaced with RhoA shows a recessive temperature‐sensitive growth phenotype. A dominant suppressor mutant was isolated from this strain. Molecular cloning of the suppressor gene revealed that the mutation occurred at the pseuodosubstrate site of PKC1, a yeast homolog of mammalian protein kinase C. Two‐hybrid analysis demonstrated that GTP‐Rho1p, but not GDP‐Rho1p, interacted with the region of Pkc1p containing the pseudosubstrate site and the C1 domain. MKK1 and MPK1 encode MAP kinase kinase and MAP kinase homologs, respectively, and function downstream of PKC1. A dominant active MKK1–6 mutation or overexpression of MPK1 suppressed the temperature sensitivity of the RhoA mutant. The dominant activating mutation of PKC1 suppressed the temperature sensitivity of the RhoA mutant. The dominant activating mutation of PKC1 suppressed the temperature sensitivity of two effector mutants of RHO1, rho1(F44Y) and rho1(E451), but not that of rho1(V43T). These results indicate that there are at least two signaling pathways regulated by Rho1p and that one of the downstream targets is Pkc1p, leading to the activation of the MAP kinase cascade.

The Src family tyrosine kinase is involved in Rho-dependent activation of c-Jun N-terminal kinase by Gα12

“…Activated mutants of RhoA, RhoB and RhoC have been shown to elevate JNK activity in 293T cells (Teramoto et al, 1996). In Saccharomyces cerevisiae, Rho1p, a homologue of the mammalian RhoA, leads to the activation of the mitogen-activated protein kinase (MAPK) cascade involved in bud formation through Pkc1p, a homologue of the mammalian protein kinase C (Nonaka et al, 1995). These reports may be in line with our observation that Rho is involved in the activation of JNK by Ga 12 .…”

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

“…Since some Gq coupled receptors have been reported to also interact with G 12/13 signaling [38][39][40][41], it is conceivable that G 12/13 signaling is activated following P2Y 6 receptor stimulation. It was also shown that Rho signaling activated PKCs [18,42,43]. These findings suggest that the activation of Rho and PKC is induced by P2Y 6 receptor activation and regulates F-actin aggregation.…”

Characterization of the interaction between RhoA and the amino‐terminal region of PKN

“…In Saccharomyces cerevisiae, the GTP-bound form of Rholp, a yeast homologue of mammalian RhoA, interacts with Pkclp, leading to the activation of the MAP kinase cascade [22]. However, there is no homology in primary amino acid sequences for the RhoA binding region between these protein kinases and PKN.…”