| Abstract: |
Human NDR1 (nuclear Dbf2-related) is a widely expressed nuclear serine-threonine kinase that has been implicated in cell proliferation and/or tumor progression. Here we present molecular characterization of the human NDR2 serine-threonine kinase, which shares ∼87% sequence identity with NDR1. NDR2 is expressed in most human tissues with the highest expression in the thymus. In contrast to NDR1, NDR2 is excluded from the nucleus and exhibits a punctate cytoplasmic distribution. The differential localization of NDR1 and NDR2 suggests that each kinase may serve distinct functions. Thus, to identify proteins that interact with NDR1 or NDR2, epitope-tagged kinases were immunoprecipitated from Jurkat T-cells. Two uncharacterized proteins that are homologous to the Saccharomyces cerevisiae kinase regulators Mob1 and Mob2 were identified. We demonstrate that NDR1 and NDR2 partially colocalize with human Mob2 in HeLa cells and confirm the NDR-Mob interactions in cell extracts. Interestingly, NDR1 and NDR2 form stable complexes with Mob2, and this association dramatically stimulates NDR1 and NDR2 catalytic activity. In summary, this work identifies a unique class of human kinase-activating subunits that may be functionally analagous to cyclins. |
| Keywords: |
protein expression; unclassified drug; human cell; cancer growth; carcinoma, hepatocellular; protein function; protein localization; cell proliferation; proteins; animals; mice; cell division; complex formation; protein protein interaction; cell protein; cell line; nerve tissue proteins; protein binding; membrane proteins; hela cell; hela cells; transfection; protein serine threonine kinase; phosphorylation; transcription factors; gene expression regulation; blotting, western; immunology; enzyme regulation; amino acid sequence; molecular sequence data; sequence homology, amino acid; cell culture; tissue distribution; thymus; tumors; saccharomyces cerevisiae; protein-serine-threonine kinases; disease progression; nucleotide sequence; epitope; immunoprecipitation; cytoplasm; plasmids; protein structure, tertiary; cell nucleus; catalysis; cycline; molecular biology; sequence homology; enzyme subunit; biochemistry; blotting, northern; enzymes; cell extracts; leukemia cell line; jurkat cells; epitopes; tumor progression; saccharomyces; precipitin tests; humans; human; priority journal; article; protein mob; protein mob2; protein ndr1; protein ndr2
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| Notes: |
J. Biol. Chem. -- Cited By (since 1996):51 -- Export Date: 16 June 2014 -- CODEN: JBCHA -- Molecular Sequence Numbers: GENBANK: AAL74055, AF206328, NP_009202, NP_031381, NP_055815, NP_443731, NP_443741, NP_775739, P07900; -- Source: Scopus |
