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A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6 and Nek7 kinases.

The Nek family of protein kinases in humans is composed of 11 members that share an amino-terminal catalytic domain related to NIMA, an Aspergillus kinase involved in the control of several aspects of mitosis, and divergent carboxyl-terminal tails of varying length. Nek6 (314AA) and Nek7 (303AA), 76% identical, have little noncatalytic sequence but bind to the carboxyl-terminal noncatalytic tail of Nercc1/Nek9, a NIMA family protein kinase that is activated in mitosis. Microinjection of anti-Nercc1 antibodies leads to spindle abnormalities and prometaphase arrest or chromosome missegregation. Herein we show that Nek6 is increased in abundance and activity during mitosis; activation requires the phosphorylation of Ser206 on the Nek6 activation loop. This phosphorylation and the activity of recombinant Nek6 is stimulated by coexpression with an activated mutant of Nercc1. Moreover, Nercc1 catalyzes the direct phosphorylation of prokaryotic recombinant Nek6 at Ser206 in vitro concomitant with 20-25-fold activation of Nek6 activity; Nercc1 activates Nek7 in vitro in a similar manner. Nercc1/Nek9 is likely to be responsible for the activation of Nek6 during mitosis and probably participates in the regulation of Nek7 as well. These findings support the conclusion that Nercc1/Nek9 and Nek6 represent a novel cascade of mitotic NIMA family protein kinases whose combined function is important for mitotic progression.

Pubmed ID: 12840024

Authors

  • Belham C
  • Roig J
  • Caldwell JA
  • Aoyama Y
  • Kemp BE
  • Comb M
  • Avruch J

Journal

The Journal of biological chemistry

Publication Data

September 12, 2003

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK17776

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Cycle Proteins
  • Cell Line
  • DNA Primers
  • Enzyme Activation
  • Humans
  • Kinetics
  • Mice
  • Mitosis
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Polymerase Chain Reaction
  • Protein-Serine-Threonine Kinases
  • Recombinant Proteins
  • Substrate Specificity