Regulatory and functional compartment of three multifunctional protein kinase systems

1979 ◽  
Vol 23 (3) ◽  
Author(s):  
Yasutomi Nishizuka ◽  
Yoshimi Takai ◽  
Eikichi Hashimoto ◽  
Akira Kishimoto ◽  
Yoshikazu Kuroda ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Multifunctional Protein

Parkinson´s related protein DJ-1 is involved in aberrant cell cycle re-entry through Cdk5

2020 ◽  
Author(s):  
Mª José López-Grueso ◽  
Carmen Alicia Padilla ◽  
José Antonio Bárcena ◽  
Raquel Requejo-Aguilar
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Cortical Neurons ◽  
Cell Cycle Progression ◽  
Cell Cycle Checkpoints ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
Multifunctional Protein ◽  
Mitogen Activated Protein ◽  
Phosphoinositide 3 Kinase

Abstract DJ-1 is a multifunctional protein involved in Parkinson disease (PD) that can act as antioxidant, molecular chaperone, protease, glyoxalase and transcriptional regulator. However, the exact mechanism by which DJ-1 dysfunction contributes to development of Parkinson´s disease remains elusive. Here, using a comparative proteomic analysis between normal cortical neurons and neurons lacking DJ-1, we show that this protein is involved in cell cycle checkpoints disruption as a consequence of increased amount of p-Tau and a-synuclein proteins, altered signalling pathways, as the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK), and deregulation of cyclin-dependent kinase 5 (Cdk5). Cdk5 is normally involved in dendritic growth, axon formation and the establishment of synapses, but can also contribute to cell cycle progression, as in our case, in pathological conditions. In addition, we observed a decrease in proteasomal activity, probably due to Tau phosphorylation that can also lead to activation of mitogenic signalling pathways. Taken together, our findings indicate, for the first time, that aborted cell cycle re-entry could be at the onset of DJ-1 associated PD. Thereby, new approaches targeting cell cycle re-entry can be envisaged to improve current therapeutic strategies.

scholarly journals The many hats of protein kinase Cδ: one enzyme with many functions

2014 ◽  
Vol 42 (6) ◽  
pp. 1529-1533 ◽  
Author(s):  
Nir Qvit ◽  
Daria Mochly-Rosen
Keyword(s):  
Protein Kinase ◽  
Physiological Response ◽  
Cellular Response ◽  
Molecular Event ◽  
Genetic Approach ◽  
Multifunctional Protein ◽  
Protein Substrates ◽  
Pathological Conditions ◽  
The Many ◽  
Protein Kinase Cδ

A large number of protein substrates are phosphorylated by each protein kinase under physiological and pathological conditions. However, it remains a challenge to determine which of these phosphorylated substrates of a given kinase is critical for each cellular response. Genetics enabled the generation of separation-of-function mutations that selectively cause a loss of one molecular event without affecting others, thus providing some tools to assess the importance of that one event for the measured physiological response. However, the genetic approach is laborious and not adaptable to all systems. Furthermore, pharmacological tools of the catalytic site are not optimal due to their non-selective nature. In the present brief review, we discuss some of the challenges in drug development that will regulate the multifunctional protein kinase Cδ (PKCδ).

scholarly journals Calmodulin-dependent multifunctional protein kinase in Aspergillus nidulans.

1988 ◽  
Vol 85 (10) ◽  
pp. 3279-3283 ◽  
Author(s):  
D. C. Bartelt ◽  
S. Fidel ◽  
L. H. Farber ◽  
D. J. Wolff ◽  
R. L. Hammell
Keyword(s):  
Protein Kinase ◽  
Aspergillus Nidulans ◽  
Multifunctional Protein

scholarly journals Identification of multifunctional ATP-citrate lyase kinase as the α-isoform of glycogen synthase kinase-3

1992 ◽  
Vol 288 (1) ◽  
pp. 309-314 ◽  
Author(s):  
K Hughes ◽  
S Ramakrishna ◽  
W B Benjamin ◽  
J R Woodgett
Keyword(s):  
Drosophila Melanogaster ◽  
Protein Kinase ◽  
Molecular Cloning ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Atp Citrate Lyase ◽  
Multifunctional Protein ◽  
Citrate Lyase ◽  
Biochemical Analyses

Multifunctional ATP-citrate lyase kinase (ACLK) exhibits several properties that are similar to glycogen-synthase kinase-3 (GSK-3). The molecular cloning of two distinct mammalian GSK-3 cDNAs and a Drosophila melanogaster (fruitfly) homologue, zeste-white3sgg, has established the existence of a GSK-3 subfamily. A multifunctional protein kinase first identified as an ACLK has recently been shown to exhibit several similarities to the alpha- and beta-forms of GSK-3. Here we have used immunological and biochemical analyses to directly compare these enzymes. Thus purified preparations of ACLK isolated from brain and liver preferentially cross-react with anti-GSK-3 alpha antisera and phosphorylate previously defined substrates of GSK-3 at identical sites. Conversely, both alpha- and beta-forms of GSK-3 phosphorylated ATP-citrate lyase at the same site(s) targeted by ACLK. These, and other similarities, demonstrate ACLK to be identical with, or highly related to, GSK-3 alpha, the implications of which are discussed.

scholarly journals Identification of calcium-calmodulin multifunctional protein kinase II in rabbit kidney

1990 ◽  
Vol 38 (1) ◽  
pp. 63-66 ◽  
Author(s):  
Rochelle M. Hanley ◽  
Shirish Shenolikar ◽  
Jo Pollack ◽  
Deborah Steplock ◽  
Edward J. Weinman
Keyword(s):  
Protein Kinase ◽  
Rabbit Kidney ◽  
Multifunctional Protein ◽  
Protein Kinase Ii

scholarly journals Calcium-dependent activation of a multifunctional protein kinase by membrane phospholipids.

1979 ◽  
Vol 254 (10) ◽  
pp. 3692-3695 ◽  
Author(s):  
Y Takai ◽  
A Kishimoto ◽  
Y Iwasa ◽  
Y Kawahara ◽  
T Mori ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Membrane Phospholipids ◽  
Multifunctional Protein ◽  
Calcium Dependent
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