NDR family of AGC kinases – essential regulators of the cell cycle and morphogenesis

Tamaskovic, Rastislav; Bichsel, Samuel J.; Hemmings, Brian A.

doi:10.1016/s0014-5793(03)00474-5

Cited by 105 publications

(128 citation statements)

References 58 publications

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“…The sequences also contained an insert of 56 amino acids between subdomains VII and VIII, and three conserved Ser/Thr residues (Fig. 3), being characteristic of the Ndr family of eukaryotic protein kinases (Tamaskovic et al 2003).…”

Section: Resultsmentioning

confidence: 99%

“…Ndr is a conserved and widely expressed nuclear protein kinase, first isolated and sequenced in humans, D. melanogaster and C. elegans (Millward et al 1995). Although an entire signal transduction cascade in which Ndr is involved has not yet been elucidated, Ndr is considered to be important for the regulation of cell growth, cell division and cell morphology (Millward et al 1999, Tamaskovic et al 2003. In the present study, three cDNA clones encoding a Ser/Thr protein kinase which is homologous to Ndr, were isolated by data mining of the wheat EST database KOMUGI, and the primary structure of these cDNAs was determined by RT-PCR and the 5′-RACE method.…”

Section: Introductionmentioning

confidence: 99%

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Cloning and Structural Analysis of Wheat cDNAs Encoding Ndr Protein Kinase Homolog by Data Mining of the EST Database KOMUGI

Imai

Terachi

2005

Breed. Sci.

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In order to gain a better understanding of the nature of nuclear dbf-related (Ndr) protein kinase homologs in monocots, three cDNA clones were isolated from common wheat (Triticum aestivum) by data mining of expressed sequence tag (EST) databases, and their primary structure was determined by reverse transcriptionpolymerase chain reaction (RT-PCR), 5′-rapid amplification of cDNA ends (RACE), and nucleotide sequencing. Deduced amino acid sequences of the cDNA clones contained all 12 highly conserved subdomains of the eukaryotic Ser/Thr protein kinase, including the ATP-binding site (in subdomain I-II) and the Ser/Thr protein kinase active-site (in subdomain VI). The sequences also contained an insert of 56 amino acids between subdomains VII and VIII, and three conserved Ser/Thr residues, being characteristic of the Ndr family of eukaryotic protein kinases. A sequence comparison among cDNAs from wheat and those from ancestral diploid species (T. boeoticum, Aegilops speltoides and Ae. squarrosa) revealed that at least three homeologous genes were expressed in hexaploid wheat. The results confirmed the usefulness of current EST databases including KOMUGI for gene cloning of wheat, since the use of specific primers designed with information about EST sequences has considerably facilitated the cloning of rare cDNAs such as Ndr.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cloning and Structural Analysis of Wheat cDNAs Encoding Ndr Protein Kinase Homolog by Data Mining of the EST Database KOMUGI

Imai

Terachi

2005

Breed. Sci.

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“…Notwithstanding the lack of dependencies in localization, the occurrence of cells with SIN phenotype in pdk1⌬ cultures suggests that Pdk1p might modulate SIN function positively. In particular, it is interesting to note that Sid2p is related to members of the AGC family of kinases (Sparks et al, 1999;Tamaskovic et al, 2003) which are known to be regulated by PDK1 family members (Belham et al, 1999). However, the finding that SIN proteins participate in correcting defects associated with the cell division apparatus (Le Goff et al, 1999;Liu et al, 1999;Mishra et al, 2004) might provide an alternate explanation to the observed synthetic lethality between pdk1⌬ and SIN mutants.…”

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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“…In mammals, there are two human homologues of dtrc, NDR1 and NDR2. The kinase domains of LATS1 and NDR1 are 52% identical, whereas LATS2 and NDR1 are 54% identical [42]. By over-expressing or suppressing human NDR1 by siRNA, the kinase has been shown to regulate centrosome duplication during the cell cycle [43].…”

Section: Ndrmentioning

confidence: 99%

Molecular characterization of human homologs of yeast MOB1

Chow

Hao

Yang

2009

Intl Journal of Cancer

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MOB (Mps One Binder) is a conserved gene family found in all major kingdoms.The MOB genes are essential components acting in mitotic exit and cytokinesis in both budding and fission yeasts. They are further identified as tumor suppressors in Drosophila (D.) melanogaster. Recently, they are found to be involved in the emerging Drosophila Hippo-LATS tumor suppressor pathway. Seven human homologs of yeast MOB (hMOB1A, 1B, 2A, 2B,3,4,5) have been discovered. The hMOB1B is the gene that has been extensively studied and is reported to be required for the activation of LATS (Large Tumor Suppressor)/NDR (Nuclear Dbf2-related) protein kinase family, however, the functional significance of the gene remains unknown. This study is the first to elucidate the biological and biochemical functions of all seven human MOBs. By examining hMOB mRNA expression in various human tissues, we found that the hMOBs have exhibited different expression patterns. We also investigated the subcellular localization of hMOBs during interphase through immunofluorescent analysis. While hMOB2A is localized in the cytoplasm, hMOB4 is exclusively found in the nucleus. All of the other hMOBs are localized in both cytoplasm and nucleus. Furthermore, we identified hMOB1A and hMOB1B as the main binding partners of LATS and NDR in vitro. Additionally, we successfully identified a region on hMOB1B for the interaction with LATS or NDR and determined the crucial residue that is responsible for the binding of LATS2 with hMOB1B. Most significantly, we found that over-expression of hMOB1B in human cancer cells inhibits cell proliferation and induces cell death.Moreover, hMOB1B when targeted to the plasma membrane dramatically enhances the iii phenotype. Conversely, small interfering (si) RNA-mediated suppression of either endogenous hMOB1A or hMOB1B causes increased cell proliferation, whereas suppression of both hMOB1A and hMOB1B demonstrates a more significant enhancement in tumor cell growth. Moreover, co-expression of both LATS and hMOB1B targeted to the plasma membrane completely abolishes cell proliferation. Our findings provide convincing evidence that hMOB1A and hMOB1B function as negative regulators of cell proliferation and as pro-apoptotic proteins. Understanding hMOBs functions in the cell and their possible role in tumorigenesis can provide important information for the diagnosis and treatment of human cancers.iv ACKNOWLEDGEMENTS

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NDR family of AGC kinases – essential regulators of the cell cycle and morphogenesis

Cited by 105 publications

References 58 publications

Cloning and Structural Analysis of Wheat cDNAs Encoding Ndr Protein Kinase Homolog by Data Mining of the EST Database KOMUGI

Cloning and Structural Analysis of Wheat cDNAs Encoding Ndr Protein Kinase Homolog by Data Mining of the EST Database KOMUGI

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

Molecular characterization of human homologs of yeast MOB1

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