PMID- 10373560
OWN - NLM
STAT- MEDLINE
DCOM- 19990722
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 7
DP  - 1999 Jul
TI  - Overproduction of human Myt1 kinase induces a G2 cell cycle delay by interfering 
      with the intracellular trafficking of Cdc2-cyclin B1 complexes.
PG  - 5113-23
AB  - The Myt1 protein kinase functions to negatively regulate Cdc2-cyclin B complexes 
      by phosphorylating Cdc2 on threonine 14 and tyrosine 15. Throughout interphase,
      human Myt1 localizes to the endoplasmic reticulum and Golgi complex, whereas
      Cdc2-cyclin B1 complexes shuttle between the nucleus and the cytoplasm. Here we
      report that overproduction of either kinase-active or kinase-inactive forms of
      Myt1 blocked the nuclear-cytoplasmic shuttling of cyclin B1 and caused cells to
      delay in the G2 phase of the cell cycle. The COOH-terminal 63 amino acids of Myt1
      were identified as a Cdc2-cyclin B1 interaction domain. Myt1 mutants lacking this
      domain no longer bound cyclin B1 and did not efficiently phosphorylate
      Cdc2-cyclin B1 complexes in vitro. In addition, cells overproducing mutant forms 
      of Myt1 lacking the interaction domain exhibited normal trafficking of cyclin B1 
      and unperturbed cell cycle progression. These results suggest that the docking of
      Cdc2-cyclin B1 complexes to the COOH terminus of Myt1 facilitates the
      phosphorylation of Cdc2 by Myt1 and that overproduction of Myt1 perturbs cell
      cycle progression by sequestering Cdc2-cyclin B1 complexes in the cytoplasm.
FAU - Liu, F
AU  - Liu F
AD  - Department of Cell Biology and Physiology, Washington University School of
      Medicine, St. Louis, Missouri 63110-1093, USA.
FAU - Rothblum-Oviatt, C
AU  - Rothblum-Oviatt C
FAU - Ryan, C E
AU  - Ryan CE
FAU - Piwnica-Worms, H
AU  - Piwnica-Worms H
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (CCNB1 protein, human)
RN  - 0 (Cyclin B)
RN  - 0 (Cyclin B1)
RN  - 0 (Membrane Proteins)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (PKMYT1 protein, human)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
SB  - IM
MH  - Binding Sites
MH  - Biological Transport
MH  - CDC2 Protein Kinase/*metabolism
MH  - Cyclin B/*metabolism
MH  - Cyclin B1
MH  - *G2 Phase
MH  - HeLa Cells
MH  - Humans
MH  - Intracellular Fluid
MH  - Membrane Proteins
MH  - Mitosis
MH  - Protein-Serine-Threonine Kinases/genetics/*metabolism
MH  - Protein-Tyrosine Kinases/genetics/*metabolism
PMC - PMC84354
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - 10.1128/mcb.19.7.5113 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Jul;19(7):5113-23. doi: 10.1128/mcb.19.7.5113.