Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Saccharomyces cerevisiae, the phosphatidylinositol kinase homologue Tor2 controls the cell-cycle-dependent organisation of the actin cytoskeleton by activating the small GTPase Rho1 via the exchange factor Rom2 [1,2]. Four Rho1 effectors are known, protein kinase C 1 (Pkc1), the formin-family protein Bni1, the glucan synthase Fks and the signalling protein Skn7 [2,3]. Rho1 has been suggested to signal to the actin cytoskeleton via Bni1 and Pkc1; rho1 mutants have never been shown to have defects in actin organisation, however [2,4]. We have further investigated the role of Rho1 in controlling actin organisation and have analysed which of the Rho1 effectors mediates Tor2 signalling to the actin cytoskeleton. We show that some, but not all, rho1 temperature-sensitive (rho1ts) mutants arrest growth with a disorganised actin cytoskeleton. Both the growth defect and the actin organisation defect of the rho1-2ts mutant were suppressed by upregulation of Pkc1 but not by upregulation of Bni1, Fks or Skn7. Overexpression of Pkc1, but not overexpression of Bni1, Fks or Skn7, also rescued a tor2ts mutant, and deletion of BNI1 or SKN7 did not prevent the suppression of the tor2ts mutation by overexpressed Rom2. Furthermore, overexpression of the Pkc1-controlled mitogen-activated protein (MAP) kinase Mpk1 suppressed the actin defect of tor2ts and rho1-2ts mutants. Thus, Tor2 signals to the actin cytoskeleton via Rho1, Pkc1 and the cell integrity MAP kinase cascade.
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PMID:The Rho1 effector Pkc1, but not Bni1, mediates signalling from Tor2 to the actin cytoskeleton. 981 7

When grown at pH 4.5, Saccharomyces cerevisiae acquires a resistance to inhibitory acetic acid levels ( approximately 0.1 M) by destabilizing Fps1p, the plasma membrane aquaglyceroporin that provides the main route for passive diffusional entry of this acid into the cell. Acetic acid stress transiently activates Hog1p mitogen-activated protein (MAP) kinase, which, in turn, phosphorylates Fps1p in order to target this channel for endocytosis and degradation in the vacuole. This activation of Hog1p is abolished with the loss of Fps1p, but is more sustained when cells express an open Fps1p channel refractory to destabilization. At neutral pH, much higher levels of acetate ( approximately 0.5 M) are needed to inhibit growth. Under such conditions, the loss of Fps1p does not abolish, but merely slows, the activation of Hog1p. Acetate stress also activates the Slt2(Mpk1)p cell integrity MAP kinase, possibly by causing inhibition of glucan synthase activity. In pH 4.5 cultures, this acetate activation of Slt2p is strongly enhanced by the loss of Fps1p and is dependent upon the cell surface sensor Wsc1p. Lack of Fps1p therefore exerts opposing effects on the activation of Hog1p and Slt2p in yeast exposed to acetic acid stress.
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PMID:Presence of the Fps1p aquaglyceroporin channel is essential for Hog1p activation, but suppresses Slt2(Mpk1)p activation, with acetic acid stress of yeast. 1960 6