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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An ATM-like gene was identified in the genome of Caenorhabditis elegans. The putative product of the gene, termed Ce-atl-1 (C. elegans ATM-like 1) consists of 2514 amino acid residues. The C-terminal sequence, which contains a PI-3 kinase-like domain, showed good homology with the products of the gene MEC1/ESR1 from budding yeast, the rad3+ gene of fission yeast and mammalian ATM (ataxia-telangiectasia and rad3+ related) genes. The results of RNA-mediated interference indicated that the major phenotype associated with repression of Ce-atl-1 was lethality (approximately 50-80%) during early embryogenesis. Among the surviving progeny, males (XO animals) arose at a high frequency (2-30%). In addition, 5% of oocyte chromosomes demonstrated aneuploidy due to a defect in pre-meiotic chromosomal segregation. Gene expression analyses indicated that Ce-atl-1 mRNA was expressed in all larval stages and that its level increased about fivefold in the adult stage. The adult expression level was decreased in the glp-4 mutant, which is defective in germ line proliferation. Ce-atl-1 was strongly expressed in both the mitotic and meiotic cells of adult gonads. In summary, Ce-atl-1 appears to be important for early embryogenesis, and loss of its function results in a defect in chromosome segregation, similar to what has been observed for AT-related proteins.
Mol Gen Genet 2000 Sep
PMID:Characterization of Ce-atl-1, an ATM-like gene from Caenorhabditis elegans. 1101 41

In budding yeast, MEC1 and RAD53 are essential for cell growth. Previously we reported that mec1 or rad53 lethality is suppressed by removal of Sml1, a protein that binds to the large subunit of ribonucleotide reductase (Rnr1) and inhibits RNR activity. To understand further the relationship between this suppression and the Sml1-Rnr1 interaction, we randomly mutagenized the SML1 open reading frame. Seven mutations were identified that did not affect protein expression levels but relieved mec1 and rad53 inviability. Interestingly, all seven mutations abolish the Sml1 interaction with Rnr1, suggesting that this interaction causes the lethality observed in mec1 and rad53 strains. The mutant residues all cluster within the 33 C-terminal amino acids of the 104-amino-acid-long Sml1 protein. Four of these residues reside within an alpha-helical structure that was revealed by nuclear magnetic resonance studies. Moreover, deletions encompassing the N-terminal half of Sml1 do not interfere with its RNR inhibitory activity. Finally, the seven sml1 mutations also disrupt the interaction with yeast Rnr3 and human R1, suggesting a conserved binding mechanism between Sml1 and the large subunit of RNR from different species.
Mol Cell Biol 2000 Dec
PMID:Mutational and structural analyses of the ribonucleotide reductase inhibitor Sml1 define its Rnr1 interaction domain whose inactivation allows suppression of mec1 and rad53 lethality. 1107 5

Doublecortin-like kinase (DCLK) shares sequence similarity to Doublecortin (DCX) in its N-terminal region. It contains the evolutionary conserved DC repeat motif as well a C-terminal kinase domain. Ectopic expression of DCLK in COS cells results in colocalization with microtubules, and phosphorylated DCLK copurifies with microtubules during assembly from embryonic brain extract. During brain development DCLK is expressed mainly in postmigratory neurons in a similar pattern to DCX. We demonstrate that DCLK is a microtubule-associated active protein kinase expressed in growth cones of postmitotic neurons.
Mol Cell Neurosci 2000 Nov
PMID:Doublecortin-like kinase is associated with microtubules in neuronal growth cones. 1108 16

Rho-type GTPases control many cytoskeletal rearrangements, but their regulation remains poorly understood. Here, we show that in S. cerevisiae, activation of the CDK Cdc28-Cln2 at bud emergence triggers relocalization of Cdc24, the GEF for Cdc42, from the nucleus to the polarization site, where it is stably maintained by binding to the adaptor Bem1. Locally activated Cdc42 then polarizes the cytoskeleton in a manner dependent on its effectors Bni1 and the PAK-like kinase Cla4. In addition, Cla4 induces phosphorylation of Cdc24, leading to its dissociation from Bem1 at bud tips, thereby ending polarized bud growth in vivo. Our results thus suggest a dynamic temporal and spatial regulation of the Cdc42 module: Cdc28-Cln triggers actin polarization by activating Cdc42, which in turn restricts its own activation via a negative feedback loop acting on its GEF Cdc24.
Mol Cell 2000 Nov
PMID:Phosphorylation of the Cdc42 exchange factor Cdc24 by the PAK-like kinase Cla4 may regulate polarized growth in yeast. 1110 54

Polo like kinase (PLK) is the kinase that was first cloned by us from the cDNA library of human placenta. It belongs to the serine/threonine kinase family and plays a very important role in cell proliferation. In this study, the localization of PLK in early human placenta in vivo was investigated. Immunostaining revealed PLK protein in syncytiotrophoblastic cells and extravillous trophoblastic cells; however proliferating cell nuclear antigen was not. It is known that cytotrophoblastic cells proliferate highly in early human placental villi; however, PLK was not detected in those cells. These results suggest that PLK plays a different role in syncytiotrophoblastic cells than it does in other proliferating cells.
Res Commun Mol Pathol Pharmacol 1999
PMID:Immunohistochemical localization of polo like kinase in early human placenta. 1112 6

We identified two mammalian ULK1 (Unc-51-like kinase involved in neurite extension) binding proteins by yeast two-hybrid screening. Both proteins showed high structural similarity to microtubule-associated protein (MAP) light chain 3 (LC3). One is identical to the Golgi-associated ATPase Enhancer of 16 kDa (GATE-16), an essential factor for intra-Golgi transport [39]. The other is identical to the gamma 2-subunit of GABA-A receptor associated protein (GABARAP) which has a possible role in receptor transport [46]. Using the yeast two-hybrid system and the in vitro GST pull-down assay, we found that the N-terminal proline/serine rich (PS) domain of ULK1 (amino acid 287-416) is required for ULK1-GATE-16 and ULK1-GABARAP protein interactions. However, the kinase activity of ULK1 affected neither ULK1-GATE-16 nor ULK1-GABARAP interaction. Immunohistochemical analysis using ULK1 and GABARAP antibodies showed that the ULK1 and the GABARAP proteins co-localized to many kind of neurons such as pyramidal cells of the hippocampus, mitral cells of the olfactory bulb, and Purkinje cells of the cerebellum. In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. These results suggest that the interaction of ULK1 and GABARAP is important to vesicle transport and axonal elongation in mammalian neurons.
Brain Res Mol Brain Res 2000 Dec 28
PMID:Interaction of the Unc-51-like kinase and microtubule-associated protein light chain 3 related proteins in the brain: possible role of vesicular transport in axonal elongation. 1114 1

In eukaryotes, the ATM and ATR family proteins play a critical role in the DNA damage and replication checkpoint controls. These proteins are characterized by a kinase domain related to the phosphatidylinositol 3-kinase, but they have the ability to phosphorylate proteins. In budding yeast, the ATR family protein Mec1/Esr1 is essential for checkpoint responses and cell growth. We have isolated the PIE1 gene in a two-hybrid screen for proteins that interact with Mec1, and we show that Pie1 interacts physically with Mec1 in vivo. Like MEC1, PIE1 is essential for cell growth, and deletion of the PIE1 gene causes defects in the DNA damage and replication block checkpoints similar to those observed in mec1Delta mutants. Rad53 hyperphosphorylation following DNA damage and replication block is also decreased in pie1Delta cells, as in mec1Delta cells. Pie1 has a limited homology to fission yeast Rad26, which forms a complex with the ATR family protein Rad3. Mutation of the region in Pie1 homologous to Rad26 results in a phenotype similar to that of the pie1Delta mutation. Mec1 protein kinase activity appears to be essential for checkpoint responses and cell growth. However, Mec1 kinase activity is unaffected by the pie1Delta mutation, suggesting that Pie1 regulates some essential function other than Mec1 kinase activity. Thus, Pie1 is structurally and functionally related to Rad26 and interacts with Mec1 to control checkpoints and cell proliferation.
Mol Cell Biol 2001 Feb
PMID:Pie1, a protein interacting with Mec1, controls cell growth and checkpoint responses in Saccharomyces cerevisiae. 1115 63

PRK1, a receptor-like kinase that is expressed in pollen, pollen tubes, and ovaries, has been shown to play important roles in pollen development and embryo sac development in Petunia inflata. We have used the kinase domain of PRK1 as a bait in the yeast two-hybrid system to identify PRK1-interacting proteins. The screening resulted in isolation of a cDNA encoding a protein highly homologous to the human and yeast beta-subunit of translation initiation factor 2B (eIF2B-beta), which was designated NeIF2Bbeta. eIF2B is a guanine nucleotide exchange protein that functions in the regulation of translation in eukaryotic cells. Deletion mutants of NeIF2Bbeta were analyzed for their interaction with PRK1, and the results suggested that the N-terminal half of NeIF2Bbeta, especially the region between residue 103 and 235, is important for the interaction. This protein association was confirmed by in vitro binding assay of the recombinant NeIF2Bbeta and PRK1 proteins. Despite high sequence homology between NeIF2Bbeta and its yeast counterpart, the NeIF2Bbeta cDNA could not rescue the phenotype of the yeast mutant strain lacking the GCD7 gene encoding eIF2B-beta, when transferred into the mutant strain.
Mol Cells 2000 Dec 31
PMID:Interaction of PRK1 receptor-like kinase with a putative elF2B beta-subunit in tobacco. 1121 66

The NeIF2Bbeta cDNA encoding beta-subunit of the translation initiation factor 2B (eIF2B-beta) was identified from Nicotiana tabacum through protein interaction with PRK1, a reproductive-organ-specific receptor-like kinase (Park et al., 2000). The eIF2B is a guanine nucleotide-exchange protein that consists of five subunits, which function in the regulation of translation in eukaryotic cells. The NeIF2Bbeta that shows a high homology in the amino acid sequence with other beta-subunits also exhibits sequence similarity to a and delta subunits of eIF2B from yeast and animals. The NeIF2Bbeta gene was expressed in all of the tissues examined, but the mRNA level was higher in reproductive tissues than in vegetative tissues. During anther development, the NeIF2Bbeta mRNA was detected in all stages with a slightly higher level in the earliest stage. The NeIF2Bbeta-GFP fusion protein was mainly localized in the cytosol.
Mol Cells 2001 Feb 28
PMID:Molecular characterization of the NeIF2Bbeta gene encoding a putative eIF2B beta-subunit in Nicotiana tabacum. 1126 12

DNA damage checkpoints lead to the inhibition of cell cycle progression following DNA damage. The Saccharomyces cerevisiae Mec1 checkpoint protein, a phosphatidylinositol kinase-related protein, is required for transient cell cycle arrest in response to DNA damage or DNA replication defects. We show that mec1 kinase-deficient (mec1kd) mutants are indistinguishable from mec1Delta cells, indicating that the Mec1 conserved kinase domain is required for all known Mec1 functions, including cell viability and proper DNA damage response. Mec1kd variants maintain the ability to physically interact with both Ddc2 and wild-type Mec1 and cause dominant checkpoint defects when overproduced in MEC1 cells, impairing the ability of cells to slow down S phase entry and progression after DNA damage in G(1) or during S phase. Conversely, an excess of Mec1kd in MEC1 cells does not abrogate the G(2)/M checkpoint, suggesting that Mec1 functions required for response to aberrant DNA structures during specific cell cycle stages can be separable. In agreement with this hypothesis, we describe two new hypomorphic mec1 mutants that are completely defective in the G(1)/S and intra-S DNA damage checkpoints but properly delay nuclear division after UV irradiation in G(2). The finding that these mutants, although indistinguishable from mec1Delta cells with respect to the ability to replicate a damaged DNA template, do not lose viability after UV light and methyl methanesulfonate treatment suggests that checkpoint impairments do not necessarily result in hypersensitivity to DNA-damaging agents.
Mol Cell Biol 2001 Jun
PMID:Characterization of mec1 kinase-deficient mutants and of new hypomorphic mec1 alleles impairing subsets of the DNA damage response pathway. 1135 99


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