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PMID:18477460

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Citation

Yamashiro, S, Yamakita, Y, Totsukawa, G, Goto, H, Kaibuchi, K, Ito, M, Hartshorne, DJ and Matsumura, F (2008) Myosin phosphatase-targeting subunit 1 regulates mitosis by antagonizing polo-like kinase 1. Dev. Cell 14:787-97

Abstract

Myosin phosphatase-targeting subunit 1 (MYPT1) binds to the catalytic subunit of protein phosphatase 1 (PP1C). This binding is believed to target PP1C to specific substrates including myosin II, thus controlling cellular contractility. Surprisingly, we found that during mitosis, mammalian MYPT1 binds to polo-like kinase 1 (PLK1). MYPT1 is phosphorylated during mitosis by proline-directed kinases including cdc2, which generates the binding motif for the polo box domain of PLK1. Depletion of PLK1 by small interfering RNAs is known to result in loss of gamma-tubulin recruitment to the centrosomes, blocking centrosome maturation and leading to mitotic arrest. We found that codepletion of MYPT1 and PLK1 reinstates gamma-tubulin at the centrosomes, rescuing the mitotic arrest. MYPT1 depletion increases phosphorylation of PLK1 at its activating site (Thr210) in vivo, explaining, at least in part, the rescue phenotype by codepletion. Taken together, our results identify a previously unrecognized role for MYPT1 in regulating mitosis by antagonizing PLK1.

Links

PubMed PMC2680213 Online version:10.1016/j.devcel.2008.02.013

Keywords

Amino Acid Sequence; Animals; CDC2 Protein Kinase/metabolism; COS Cells; Cell Cycle Proteins/antagonists & inhibitors; Cell Cycle Proteins/metabolism; Cell Survival; Centrosome/enzymology; Cercopithecus aethiops; Enzyme Activation; HeLa Cells; Humans; Kinetochores/enzymology; Mitosis; Mitotic Spindle Apparatus/enzymology; Molecular Sequence Data; Myosin-Light-Chain Phosphatase/chemistry; Myosin-Light-Chain Phosphatase/metabolism; Phosphorylation; Phosphothreonine/metabolism; Protein Binding; Protein Transport; Protein-Serine-Threonine Kinases/antagonists & inhibitors; Protein-Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins/antagonists & inhibitors; Proto-Oncogene Proteins/metabolism; Rats; Tubulin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:MYPT1

located_in

GO:0005813: centrosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MYPT1

located_in

GO:0000776: kinetochore

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CDK1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O14974

F

Seeded From UniProt

complete

HUMAN:PLK1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O14974

F

Seeded From UniProt

complete

HUMAN:PLK1

located_in

GO:0005813: centrosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PLK1

located_in

GO:0000776: kinetochore

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MYPT1

involved_in

GO:0006470: protein dephosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYPT1

involved_in

GO:0000278: mitotic cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYPT1

part_of

GO:0000776: kinetochore

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MYPT1

part_of

GO:0005813: centrosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MYPT1

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P06493

F

Seeded From UniProt

complete

HUMAN:MYPT1

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P53350

F

Seeded From UniProt

complete

HUMAN:MYPT1

enables

GO:0019208: phosphatase regulator activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MYPT1

involved_in

GO:0007098: centrosome cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PLK1

part_of

GO:0005813: centrosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PLK1

enables

GO:0004674: protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PLK1

part_of

GO:0000776: kinetochore

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PLK1

involved_in

GO:0000278: mitotic cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PLK1

involved_in

GO:0007098: centrosome cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CDK1

enables

GO:0004693: cyclin-dependent protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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