Human Mob proteins regulate the NDR1 and NDR2 serine-threonine kinases.
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 approximately 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.
Devroe
Eric
E
Department of Systems Biology, Harvard Medical School, The Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Erdjument-Bromage
Hediye
H
Tempst
Paul
P
Silver
Pamela A
PA
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002384:Catalysis; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D000939:Epitopes / Q000737:chemistry; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055456:Nodal Signaling Ligands; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D017855:Transferases (Other Substituted Phosphate Groups)
D000939:Epitopes; D008565:Membrane Proteins; C113775:Ndr2 protein, vertebrate; D009419:Nerve Tissue Proteins; D055456:Nodal Signaling Ligands; D011506:Proteins; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C491614:STK38 protein, human; C455440:SGMS1 protein, human; D017855:Transferases (Other Substituted Phosphate Groups)