A Schizosaccharomyces pombe gene, ksg1, that shows structural homology to the human phosphoinositide-dependent protein kinase PDK1, is essential for growth, mating and sporulation

Niederberger, Christian; Schweingruber, M. Ernst

doi:10.1007/s004380050955

Cited by 55 publications

(54 citation statements)

References 30 publications

(28 reference statements)

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“…In fission yeast, Ksg1 is known as a homolog of PDK1 (Niederberger and Schweingruber, 1999). We therefore examined the role of Ksg1 in phosphorylation and activity of Psk1 using the temperature-sensitive (ts) mutants of two distinct ksg1 alleles (ts208 and ts358).…”

Section: S6 Kinase In Fission Yeast 5843mentioning

confidence: 99%

Psk1, an AGC kinase family member in fission yeast, is directly phosphorylated and controlled by TORC1 and functions as S6 kinase

Nakashima

Otsubo

Yamashita

et al. 2012

Journal of Cell Science

102

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SummaryTarget of rapamycin (TOR), an evolutionarily conserved serine/threonine protein kinase, plays pivotal roles in several important cellular processes in eukaryotes. In the fission yeast Schizosaccharomyces pombe, TOR complex 1 (TORC1), which includes Tor2 as a catalytic subunit, manages the switch between cell proliferation and differentiation by sensing nutrient availability. However, little is known about the direct target of TORC1 that plays key roles in nutrient-dependent TORC1 signaling in fission yeast. Here we report that in fission yeast, three AGC kinase family members, named Psk1, Sck1 and Sck2, which exhibit high homology with human S6K1, are phosphorylated under nutrient-rich conditions and are dephosphorylated by starvation conditions. Among these, Psk1 is necessary for phosphorylation of ribosomal protein S6. Furthermore, Psk1 phosphorylation is regulated by TORC1 in nutrient-dependent and rapamycin-sensitive manners in vivo. Three conserved regulatory motifs (the activation loop, the hydrophobic and the turn motifs) in Psk1 are phosphorylated and these modifications are required for Psk1 activity. In particular, phosphorylation of the hydrophobic motif is catalyzed by TORC1 in vivo and in vitro. Ksg1, a homolog of PDK1, is also important for Psk1 phosphorylation in the activation loop and for its activity. The TORC1 components Pop3, Toc1 and Tco89, are dispensable for Psk1 regulation, but disruption of pop3 + causes an increase in the sensitivity of TORC1 to rapamycin. Taken together, these results provide convincing evidence that TORC1/Psk1/Rps6 constitutes a nutrient-dependent signaling pathway in fission yeast.

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Section: S6 Kinase In Fission Yeast 5843mentioning

confidence: 99%

Psk1, an AGC kinase family member in fission yeast, is directly phosphorylated and controlled by TORC1 and functions as S6 kinase

Nakashima

Otsubo

Yamashita

et al. 2012

Journal of Cell Science

102

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“…S. cerevisiae has two PDK1 genes, PKH1 and PKH2, which are required for cell growth and viability . Similarly, the S. pombe homologue, ksg1, is required for growth, and also for mating and sporulation (Niederberger & Schweingruber 1999). The C. elegans homologue has multiple phenotypic effects, including the induction of diapause at the dauer larval stage and increased lifespan (Paradis et al 1999).…”

Section: S6kmentioning

confidence: 99%

The Dstpk61 locus of Drosophila produces multiple transcripts and protein isoforms, suggesting it is involved in multiple signalling pathways

Clyde

Bownes

2000

Journal of Endocrinology

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The Drosophila gene Dstpk61 encodes a serine threonine protein kinase homologous to human phosphoinositidedependent protein kinase (PDK1), and also has homologues in S. cerevisiae, S. pombe, C. elegans, A. thaliana, mouse, and sheep. Where its function has been investigated, this kinase is thought to be involved in regulating cell growth and survival in response to extracellular signals such as insulin and growth factors. In Drosophila it produces multiple transcripts, some of which appear to be sex-specific.In addition to the five Dstpk61 cDNAs we have described previously we report the existence of a further 18 expressed sequence tag (EST) cDNAs, three of which we have fully sequenced. We conclude that Dstpk61 is a complex locus that utilises a combination of alternative promoters, alternative splice sites and alternative polyadenylation sites to produce a vast array of different transcripts. These cDNAs encode at least four different DSTPK61 protein isoforms with variant N-termini. In this paper, we discuss the possible functions of the distinct Dstpk61 transcripts and how they might be differentially regulated. We also discuss the roles that DSTPK61 protein isoforms might play in relation to the protein domains they contain and their potential targets in the cell. Finally, we report the putative structure of the human PDK1 gene based on computer comparisons of available mRNA and genomic sequences. The value of using sequence data from other species for experimental design in mammalian systems is discussed.

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“…According to our results obtained from the sequence analysis, S. pombe Pdk1p is most related to Pkh1p and does not contain detectable PH domains. There is an additional PDK1-like protein in fission yeast, termed Ksg1, and its function is required for meiosis and growth (Niederberger and Schweingruber, 1999;Matsuo et al, 2003;Tang and McLeod, 2004), whereas Pdk1p is important for aspects of mitosis and cytokinesis.…”

Section: Discussionmentioning

confidence: 99%

Roles of Pdk1p, a Fission Yeast Protein Related to Phosphoinositide-dependent Protein Kinase, in the Regulation of Mitosis and Cytokinesis

Bimbó

Liu

Balasubramanian

2005

MBoC

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Proteins related to the phosphoinositide-dependent protein kinase family have been identified in the majority of eukaryotes. Although much is known about upstream mechanisms that regulate the PDK1-family of kinases in metazoans, how these kinases regulate cell growth and division remains unclear. Here, we characterize a fission yeast protein related to members of this family, which we have termed Pdk1p. Pdk1p localizes to the spindle pole body and the actomyosin ring in early mitotic cells. Cells deleted for pdk1 display multiple defects in mitosis and cytokinesis, all of which are exacerbated when the function of fission yeast polo kinase, Plo1p, is partially compromised. We conclude that Pdk1p functions in concert with Plo1p to regulate multiple processes such as the establishment of a bipolar mitotic spindle, transition to anaphase, placement of the actomyosin ring and proper execution of cytokinesis. We also present evidence that the effects of Pdk1p on cytokinesis are likely mediated via the fission yeast anillin-related protein, Mid1p, and the septation initiation network. INTRODUCTIONThe segregation of chromosomes during mitosis and the physical division of cells during cytokinesis represent two irreversible events in the cell cycle. Not surprisingly, mitosis and cytokinesis are tightly regulated in the cell cycle in such a way that mitosis is initiated only upon completion of DNA synthesis and cytokinesis is executed only after completion of mitosis.The fission yeast Schizosaccharomyces pombe has been used extensively for the study of mitosis and cytokinesis, due to the structural and molecular conservation of these events in fission yeast and metazoans (Nurse 1990;Gould and Simanis, 1997;Feierbach and Chang, 2001). S. pombe has three chromosomes that condense during mitosis and are separated along an intranuclear mitotic spindle (Yanagida, 1998). After chromosome segregation, S. pombe cells divide through the use of an actomyosin-based contractile ring. Gene products important for mitotic entry, mitotic progression, and cytokinesis have been identified from a number of genetic screens, as well as from reverse genetic approaches (Nurse et al., 1976;Hirano et al., 1986;Chang et al., 1996;Balasubramanian et al., 1998). Central to the regulation of mitosis and cytokinesis are the S. pombe polo-related protein kinase Plo1p (Ohkura et al., 1995;Bähler et al., 1998;Mulvihill et al., 1999) and members of the septation initiation network (SIN), a signaling pathway comprised of three protein kinases (Cdc7p, Sid1p, and Sid2p) and a GTPase (Spg1p) Rajagopalan et al., 2003). Members of the polo-kinase family are conserved across all eukaryotes (Nigg, 1998). In addition, several components of the SIN are highly conserved, including an analogous signaling complex in the budding yeast referred to as the mitotic exit network (Bardin and Amon, 2001;McCollum and Gould, 2001;Simanis, 2003). The fission yeast Plo1p-kinase and SIN components localize to the spindle pole body and coordinate mitotic events with cytokinesis .To...

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A Schizosaccharomyces pombe gene, ksg1, that shows structural homology to the human phosphoinositide-dependent protein kinase PDK1, is essential for growth, mating and sporulation

Cited by 55 publications

References 30 publications

Psk1, an AGC kinase family member in fission yeast, is directly phosphorylated and controlled by TORC1 and functions as S6 kinase

Psk1, an AGC kinase family member in fission yeast, is directly phosphorylated and controlled by TORC1 and functions as S6 kinase

The Dstpk61 locus of Drosophila produces multiple transcripts and protein isoforms, suggesting it is involved in multiple signalling pathways

Roles of Pdk1p, a Fission Yeast Protein Related to Phosphoinositide-dependent Protein Kinase, in the Regulation of Mitosis and Cytokinesis

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