Pom1 kinase recruited to cell ends by the Tea1-Tea4/Wsh3 complex is essential for proper localization of a GAP for Cdc42, Rga4, which ensures bipolar localization of GTP-bound, active Cdc42. Because of the established role of Cdc42 in F-actin formation, these observations provide a new insight into how the microtubule system achieves localized formation of F-actin to generate cell polarity.

Wsh3/Tea4 is an essential component of the Tea1 cell-end complex. In addition to its role in bipolar growth during the normal cell cycle, the Wsh3-Tea1 complex, together with the stress-signaling MAPK cascade, contributes to cell-polarity maintenance under stress conditions.

Members of the mitogen-activated protein kinase (MAPK) subfamily responsive to environmental stress stimuli are known as SAPKs (stress-activated protein kinases), which are conserved from yeast to humans. In the fission yeast Schizosaccharomyces pombe, Spc1/Sty1 SAPK is activated by diverse forms of stress, such as osmostress, oxidative stress and heat shock, and induces gene expression through the Atf1 transcription factor. Sin1 (SAPK interacting protein 1) was originally isolated as a protein that interacts with Spc1, and its orthologs were also found in diverse eukaryotes. Here we report that Sin1 is not required for the stress gene expression regulated by Spc1 and Atf1, and that Sin1 is an essential component of TOR (target of rapamycin) complex 2 (TORC2). TORC2 is not essential for cell viability in S. pombe but plays important roles in cellular survival of stress conditions through phosphorylation and activation of an AGC-family protein kinase, Gad8. In addition, inactivation of Gad8 results in a synthetic growth defect with cdc25-22, a temperature-sensitive mutation of the Cdc25 phosphatase that activates Cdc2 kinase at G 2 /M. Gad8 also positively regulates expression of the CDK inhibitor gene rum1 + , which is essential for cell cycle arrest in G 1 after nitrogen starvation. These results strongly suggest that the TORC2-Gad8 pathway has multiple physiological functions in cellular stress resistance and cell cycle progression at both G 1 /S and G 2 /M transitions. IntroductionStress-activated protein kinases (SAPKs) form an evolutionarily conserved subfamily of the MAP kinase (MAPK), members of which are stimulated in response to environmental stress. The prototype of SAPK was first identified in budding yeast as Hog1, which is mainly activated by high osmolarity stress. 1 On the other hand, human JNK (c-Jun N-terminal Kinase) and p38 SAPKs 2 as well as Spc1/Sty1 in the fission yeast Schizosaccharomyces pombe 3 are activated in response to diverse forms of stress, including osmostress, heat shock, oxidative stress and nutritional starvation. In S. pombe, activated Spc1 induces expression of a set of stress resistance genes through the Atf1 transcription factor. [4][5][6] Cells lacking the functional Spc1-Atf1 pathway are hypersensitive to diverse forms of stress conditions, indicating the essential role of the SAPK signaling in cellular survival of environmental changes. In addition, Spc1 positively regulates the initiation of mitosis independently of the Atf1-regulated gene expression. [7][8][9] Sin1 (SAPK interacting protein 1) was isolated by a yeast twohybrid screen as a protein that interacts with Spc1 MAPK. 10 It was reported that a sin1 mutant was hypersensitive to various stress conditions and defective in the stress gene expression regulated by the Spc1-Atf1 pathway and that by Pap1, an AP-1 family transcription factor. 10 Sin1 is widely conserved among eukaryotic species, 11,12 and its mammalian ortholog also interacts with JNK SAPK 13 and MEKK2 MAPK kinase kinase. 14 More recently, however, Si...

Background: In mammals, proteins containing BIR domains (IAPs and survivin) are implicated in inhibiting apoptosis and sister chromatid separation. In the nematode, Bir1 is required for a proper localization of aurora kinase, which moves from the mitotic chromosome in metaphase to the spindle midzone in anaphase as a passenger. Fission yeast Bir1/Pbh1 is essential for normal mitosis.

Target of rapamycin (TOR) is an evolutionarily conserved protein kinase that controls multiple cellular processes upon various intracellular and extracellular stimuli. Since its first discovery, extensive studies have been conducted both in yeast and animal species including humans. Those studies have revealed that TOR forms two structurally and physiologically distinct protein complexes; TOR complex 1 (TORC1) is ubiquitous among eukaryotes including animals, yeast, protozoa, and plants, while TOR complex 2 (TORC2) is conserved in diverse eukaryotic species other than plants. The studies have also identified two crucial regulators of mammalian TORC1 (mTORC1), Ras homolog enriched in brain (RHEB) and RAG GTPases. Of these, RAG regulates TORC1 in yeast as well and is conserved among eukaryotes with the green algae and land plants as apparent exceptions. RHEB is present in various eukaryotes but sporadically missing in multiple taxa. RHEB, in the budding yeast Saccharomyces cerevisiae, appears to be extremely divergent with concomitant loss of its function as a TORC1 regulator. In this review, we summarize the evolutionarily conserved functions of the key regulatory subunits of TORC1 and TORC2, namely RAPTOR, RICTOR, and SIN1. We also delve into the evolutionary conservation of RHEB and RAG and discuss the conserved roles of these GTPases in regulating TORC1.