NDR kinases regulate essential cell processes from yeast to humans

Hergovich, Alexander; Stegert, Mario; Schmitz, Debora; Hemmings, Brian A.

doi:10.1038/nrm1891

Cited by 308 publications

(464 citation statements)

References 130 publications

Supporting

Mentioning

446

Contrasting

Unclassified

Order By: Relevance

“…Considering the impact of initial studies on the Ste20-like Hippo kinase [26,[55][56][57][58], Hippo/Mats/Lats signalling has been referred to as Hippo signalling ever since. Intriguingly, the Hippo pathway is very similar to the MEN/SIN cascades in budding and fission yeast [15,16,33]. As reported for the MEN/SIN, a GCK-II Ste20-like kinase activates a LATS/NDR kinase in complex with a MOB1 protein.…”

Section: Hippo Signalling In G2/m In Drosophila Melanogastermentioning

confidence: 75%

“…In flies, members of the Ste20-like kinase, LATS/NDR, and MOB protein families have essential tumour suppressive roles by co-ordination cell growth, proliferation and death [16,[21][22][23]. Considering the impact of initial studies on the Ste20-like Hippo kinase [26,[55][56][57][58], Hippo/Mats/Lats signalling has been referred to as Hippo signalling ever since.…”

Section: Hippo Signalling In G2/m In Drosophila Melanogastermentioning

confidence: 99%

“…The conserved signalling core cassettes function as follows: Cdc15p and Sid1p (the budding and fission yeast Ste20-like kinase counterparts of Drosophila Hippo) activate Mob1p (the yeast counterpart of Mats/dMOB1) in complex with Dbf2p or Sid2p (the LATS/NDR kinase counterparts of Warts/Lats and Trc), which in turn leads to the activation of protein phosphatase Cdc14p and Clp1p, respectively. Although in yeast additional Ste20-like kinases, LATS/NDR kinases, and MOB proteins are expressed [15,16], the functionality of MEN and SIN is fully dependent on one single signalling core module composed of specific members of the Ste20-like kinase, LATS/NDR, and MOB protein families, namely Cdc15p/ Mob1p/Dbf2p and Sid1p/Mob1p/Sid2p, respectively.…”

Section: Septation Initiation Network (Sin) In Schizosaccharomyces Pombementioning

confidence: 99%

“…When comparing Hippo signalling with the MEN/SIN, one should also mention the conservation of scaffolding proteins between these pathways [16]. In budding and fission yeast, the scaffolding proteins Nud1p and Cdc11p/Sid4p support MEN and SIN signalling, respectively [10,11,16].…”

Section: Hippo Signalling In G2/m In Drosophila Melanogastermentioning

confidence: 99%

“…Since mitotic CDK1 inhibits cytokinesis and abscission (cell cleavage) in fungi and metazoans, these studies also suggested that the MEN/SIN controls not only mitotic exit (progression from anaphase to late telophase), but can also play a role in the regulation of cytokinesis and abscission. Intriguingly, the core signalling module of the MEN/SIN is composed of highly conserved members of the Ste20-like kinase family [12][13][14], the MOB co-activator protein family [15], the LATS/NDR kinase family [16,17], and the Cdc14 protein phosphatase family [18]. The MEN/SIN pathway is very highly conserved from yeast to humans, since human Cdc14 can even compensate for the loss of Cdc14 in budding and fission yeast [19,20].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Hippo signalling in the G2/M cell cycle phase: Lessons learned from the yeast MEN and SIN pathways

Hergovich

Hemmings

2012

Seminars in Cell & Developmental Biology

Self Cite

View full text Add to dashboard Cite

Over the past decade Hippo kinase signalling has been established as an essential tumour suppressor pathway controlling tissue growth in flies and mammals. All members of the Hippo core signalling cassette are conserved from yeast to humans, whereby the yeast analogues of Hippo, Mats and Lats are central components of the mitotic exit network and septation initiation network in budding and fission yeast, respectively. Here, we discuss how far core Hippo signalling components in Drosophila melanogaster and mammals have reported similar mitotic functions as already established for their highly conserved yeast counterparts.

show abstract

Section: Hippo Signalling In G2/m In Drosophila Melanogastermentioning

confidence: 75%

Section: Hippo Signalling In G2/m In Drosophila Melanogastermentioning

confidence: 99%

Section: Septation Initiation Network (Sin) In Schizosaccharomyces Pombementioning

confidence: 99%

Section: Hippo Signalling In G2/m In Drosophila Melanogastermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hippo signalling in the G2/M cell cycle phase: Lessons learned from the yeast MEN and SIN pathways

Hergovich

Hemmings

2012

Seminars in Cell & Developmental Biology

Self Cite

View full text Add to dashboard Cite

show abstract

Trypanosomatid Cell Division Kinases

Benz

Thomas

Hammarton

2013

Protein Phosphorylation in Parasites

View full text Add to dashboard Cite

Advances have been made recently in understanding the order of events in the cell division cycles of Leishmania spp. and Trypanosoma cruzi, adding to previous knowledge of events in Trypanosoma brucei, and highlighting similarities and differences between these trypanosomatids. However, the present understanding of how the cell cycle is regulated by kinases still largely derives from analyses in T. brucei, since convenient genetic tools for analyzing the function of essential regulators -for example, inducible expression systems and/or RNA interferenceare still lacking in Leishmania and T. cruzi. While current understanding of the function of some kinases (e.g., some cyclin-dependent kinases, the NDR kinases, aurora, tousled-like and polo-like kinases) is now very good, many more remain to be characterized, as do details of the signal transduction pathways in which they operate. A number of protein kinases have, in recent years, been genetically -and in some cases also chemically -validated as potential novel drug targets for human African trypanosomiasis or leishmaniasis, although only a few, including CRK3: CYC6, CRK3:CYCA, the NDR kinases, PK50 and PK53 and polo-like kinase, have been subjected to high-throughput screening to identify small-molecule inhibitors. However, problems with these screens include a failure to identify potent inhibitors against the parasite enzyme in vitro, a lack of selectivity for the parasite enzyme over the equivalent human enzyme, or poor efficacy against the parasite. Thus, further chemical investigations will be required to generate new compounds with more ideal properties.

show abstract

Kinetoplastid AGC Kinases

Bachmaier

Boshart

2013

Protein Phosphorylation in Parasites

View full text Add to dashboard Cite

Genes encoding protein kinases homologous to the AGC (PKA-PKG-PKC-like) group are relatively under-represented in trypanosomatid genomes, and most of them cannot be assigned to one of the subfamilies conserved in higher organisms, as illustrated by the zinc finger kinase ZFK, a kinase with unique and kinetoplastid-specific domain architecture outside the catalytic core. Second messenger-regulated kinases are apparently absent, like the PKC and PKG subfamilies, or have controversial ligand-binding properties, like PKA. Hence, the AGC group is very unconventional in kinetoplastids. Only the nuclear DBF2-related (NDR) kinases PK50 and PK53 are currently being prioritized for drug development. In this chapter the currently available knowledge on AGC kinases is reviewed, and the suggestion made that further investigations of this group of kinases will most likely deliver parasite-specific kinase drug targets.

show abstract

NDR kinases regulate essential cell processes from yeast to humans

Cited by 308 publications

References 130 publications

Hippo signalling in the G2/M cell cycle phase: Lessons learned from the yeast MEN and SIN pathways

Hippo signalling in the G2/M cell cycle phase: Lessons learned from the yeast MEN and SIN pathways

Trypanosomatid Cell Division Kinases

Kinetoplastid AGC Kinases

Contact Info

Product

Resources

About