scholarly journals Protein Kinase C-Regulated AβProduction and Clearance

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Taehyun Kim ◽  
David J. Hinton ◽  
Doo-Sup Choi
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Mapk Pathway ◽  
The Elderly ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Kinase C ◽  
Secretase Activity ◽  
Mitogen Activated Protein ◽  
The Brain

Alzheimer’s disease (AD) is the most common form of dementia among the elderly population. AD, which is characterized as a disease of cognitive deficits, is mainly associated with an increase of amyloidβ-peptide (Aβ) in the brain. A growing body of recent studies suggests that protein kinase C (PKC) promotes the production of the secretory form of amyloid precursor protein (sAPPα) via the activation ofα-secretase activity, which reduces the accumulation of pathogenic Aβlevels in the brain. Moreover, activation of PKCαand mitogen-activated protein kinase (MAPK) is known to increase sAPPα. A novel type of PKC, PKCε, activates the Aβdegrading activity of endothelin converting enzyme type 1 (ECE-1), which might be mediatedviathe MAPK pathway as well. Furthermore, dysregulation of PKC-MAPK signaling is known to increase Aβlevels in the brain, which results in AD phenotypes. Here, we discuss roles of PKC in Aβproduction and clearance and its implication in AD.

scholarly journals Platelet-derived growth factor activation of mitogen-activated protein kinase depends on the sequential activation of phosphatidylcholine-specific phospholipase C, protein kinase C-ζ and Raf-1

1997 ◽  
Vol 325 (2) ◽  
pp. 303-307 ◽  
Author(s):  
Marc C. M. VAN DIJK ◽  
Henk HILKMANN ◽  
Wim J. VAN BLITTERSWIJK
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Platelet Derived Growth Factor ◽  
Kinase C ◽  
Mitogen Activated Protein ◽  
Pkc Ζ

The mechanism of Raf-1 activation by platelet-derived growth factor (PDGF) is poorly defined. We previously reported that, in Rat-1 fibroblasts, PDGF activates a phosphatidylcholine-specific phospholipase C (PC-PLC) and that the product, diacylglycerol, somehow activates protein kinase C-ζ (PKC-ζ). Both PC-PLC and PKC-ζ activities were required for PDGF activation of mitogen-activated protein kinase (MAPK). Now we report that MAPK activation by exogenous PC-PLC depends on Raf-1 activation. PKC-ζ co-immunoprecipitates with, phoshorylates and activates Raf-1, suggesting that in the PDGF- and PC-PLC-activated MAPK pathway, PKC-ζ operates in a signalling complex as a direct activator of Raf-1.

scholarly journals Cdc37p Is Required for Stress-Induced High-Osmolarity Glycerol and Protein Kinase C Mitogen-Activated Protein Kinase Pathway Functionality by Interaction with Hog1p and Slt2p (Mpk1p)

2007 ◽  
Vol 6 (3) ◽  
pp. 521-532 ◽  
Author(s):  
Patricija Hawle ◽  
Danielle Horst ◽  
Jan Paul Bebelman ◽  
Xiao Xian Yang ◽  
Marco Siderius ◽  
...  
Keyword(s):  
Cell Wall ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Hog Pathway ◽  
High Osmolarity ◽  
High Osmolarity Glycerol ◽  
Kinase C ◽  
Mitogen Activated Protein

ABSTRACT The yeast Saccharomyces cerevisiae utilizes rapidly responding mitogen-activated protein kinase (MAPK) signaling cascades to adapt efficiently to a changing environment. Here we report that phosphorylation of Cdc37p, an Hsp90 cochaperone, by casein kinase 2 controls the functionality of two MAPK cascades in yeast. These pathways, the high-osmolarity glycerol (HOG) pathway and the cell integrity (protein kinase C) MAPK pathway, mediate adaptive responses to high osmotic and cell wall stresses, respectively. Mutation of the phosphorylation site Ser14 in Cdc37p renders cells sensitive to osmotic stress and cell wall perturbation by calcofluor white. We found that levels of the MAPKs Hog1p and Slt2p (Mpk1p) in cells are reduced in a cdc37-S14A mutant, and consequently downstream responses mediated by Hog1p and Slt2p are compromised. Furthermore, we present evidence that Hog1p and Slt2p both interact in a complex with Cdc37p in vivo, something that has not been reported previously. The interaction of Hsp90, Slt2p, and Hog1p with Cdc37p depends on the phosphorylation status of Cdc37p. In fact, our biochemical data show that the osmosensitive phenotype of the cdc37-S14A mutant is due to the loss of the interaction between Cdc37p, Hog1p, and Hsp90. Likewise, during cell wall stress, the interaction of Slt2p with Cdc37p and Hsp90 is crucial for Slt2p-dependent downstream responses, such as the activation of the transcription factor Rlm1p. Interestingly, phosphorylated Slt2p, but not phosphorylated Hog1p, has an increased affinity for Cdc37p. Together these observations suggest that Cdc37p acts as a regulator of MAPK signaling.

Sign in / Sign up

Export Citation Format

Share Document