scholarly journals Antizyme Restrains Centrosome Amplification by Regulating the Accumulation of Mps1 at Centrosomes

2010 ◽  
Vol 21 (22) ◽  
pp. 3878-3889 ◽  
Author(s):  
Christopher Kasbek ◽  
Ching-Hui Yang ◽  
Harold A. Fisk
Keyword(s):  
Protein Kinase ◽  
Tumor Suppressor ◽  
Centrosome Amplification ◽  
Centrosome Duplication ◽  
Early Event ◽  
Mitotic Spindles ◽  
Duplication Cycle

Extra centrosomes are found in many tumors, and their appearance is an early event that can generate aberrant mitotic spindles and aneuploidy. Because the failure to appropriately degrade the Mps1 protein kinase correlates with centrosome overproduction in tumor-derived cells, defects in the factors that promote Mps1 degradation may contribute to extra centrosomes in tumors. However, while we have recently characterized an Mps1 degradation signal, the factors that regulate Mps1 centrosomal Mps1 are unknown. Antizyme (OAZ), a mediator of ubiquitin-independent degradation and a suspected tumor suppressor, was recently shown to localize to centrosomes and modulate centrosome overproduction, but the known OAZ substrates were not responsible for its effect on centrosomes. We have found that OAZ exerts its effect on centrosomes via Mps1. OAZ promotes the removal of Mps1 from centrosomes, and centrosome overproduction caused by reducing OAZ activity requires Mps1. OAZ binds to Mps1 via the Mps1 degradation signal and modulates the function of Mps1 in centrosome overproduction. Moreover, OAZ regulates the canonical centrosome duplication cycle, and reveals a function for Mps1 in procentriole assembly. Together, our data suggest that OAZ restrains the assembly of centrioles by controlling the levels of centrosomal Mps1 through the Cdk2-regulated Mps1 degradation signal.

Protein Kinase Translocation as an Early Event in the Hormonal Control of Uterine Contraction

Science ◽  
1974 ◽  
Vol 183 (4123) ◽  
pp. 430-432 ◽  
Author(s):  
S. G. Korenman ◽  
R. C. Bhalla ◽  
B. M. Sanborn ◽  
R. H. Stevens
Keyword(s):  
Protein Kinase ◽  
Uterine Contraction ◽  
Hormonal Control ◽  
Early Event

scholarly journals Tumor suppressor death-associated protein kinase 1 inhibits necroptosis by p38 MAPK activation

2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Yung-Hsuan Wu ◽  
Ting-Fang Chou ◽  
Leslie Young ◽  
Fu-Yi Hsieh ◽  
Hsuan-Yin Pan ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Tumor Suppressor ◽  
P38 Mapk ◽  
Mapk Activation ◽  
Death Associated Protein Kinase

The centrosome duplication cycle and the cell division cycle

1992 ◽  
Vol 76 (2) ◽  
pp. 218-218
Author(s):  
Tournier Frédéric ◽  
Bailly Eric ◽  
Bornens Michel
Keyword(s):  
Cell Division ◽  
Cell Division Cycle ◽  
Centrosome Duplication ◽  
Duplication Cycle

scholarly journals Integrin-mediated Protein Kinase A Activation at the Leading Edge of Migrating Cells

2008 ◽  
Vol 19 (11) ◽  
pp. 4930-4941 ◽  
Author(s):  
Chinten J. Lim ◽  
Kristin H. Kain ◽  
Eugene Tkachenko ◽  
Lawrence E. Goldfinger ◽  
Edgar Gutierrez ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Leading Edge ◽  
Pi3 Kinase ◽  
Early Event ◽  
Type I ◽  
Cell Protrusion ◽  
Kinase A ◽  
Migrating Cells

cAMP-dependent protein kinase A (PKA) is important in processes requiring localized cell protrusion, such as cell migration and axonal path finding. Here, we used a membrane-targeted PKA biosensor to reveal activation of PKA at the leading edge of migrating cells. Previous studies show that PKA activity promotes protrusion and efficient cell migration. In live migrating cells, membrane-associated PKA activity was highest at the leading edge and required ligation of integrins such as α4β1 or α5β1 and an intact actin cytoskeleton. α4 integrins are type I PKA-specific A-kinase anchoring proteins, and we now find that type I PKA is important for localization of α4β1 integrin-mediated PKA activation at the leading edge. Accumulation of 3′ phosphorylated phosphoinositides [PtdIns(3,4,5)P3] products of phosphatidylinositol 3-kinase (PI3-kinase) is an early event in establishing the directionality of migration; however, polarized PKA activation did not require PI3-kinase activity. Conversely, inhibition of PKA blocked accumulation of a PtdIns(3,4,5)P3-binding protein, the AKT-pleckstrin homology (PH) domain, at the leading edge; hence, PKA is involved in maintaining cell polarity during migration. In sum, we have visualized compartment-specific PKA activation in migrating cells and used it to reveal that adhesion-mediated localized activation of PKA is an early step in directional cell migration.

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