scholarly journals Preheating Accelerates Mitogen-activated Protein (MAP) Kinase Inactivation Post-heat Shock via a Heat Shock Protein 70-mediated Increase in Phosphorylated MAP Kinase Phosphatase-1

2005 ◽  
Vol 280 (13) ◽  
pp. 13179-13186 ◽  
Author(s):  
Kyoung-Hee Lee ◽  
Choon-Taek Lee ◽  
Young Whan Kim ◽  
Sung Koo Han ◽  
Young-Soo Shim ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Map Kinase ◽  
Heat Shock Protein 70 ◽  
Map Kinase Phosphatase ◽  
Protein Map ◽  
Mitogen Activated Protein

scholarly journals The Molecular Chaperone Heat Shock Protein 70 Controls Liver Cancer Initiation and Progression by Regulating Adaptive DNA Damage and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling Pathways

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Wonkyoung Cho ◽  
Xiongjie Jin ◽  
Junfeng Pang ◽  
Yan Wang ◽  
Nahid F. Mivechi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Heat Shock ◽  
Protein Kinase ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Cell Transformation ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT Delineating the mechanisms that drive hepatic injury and hepatocellular carcinoma (HCC) progression is critical for development of novel treatments for recurrent and advanced HCC but also for the development of diagnostic and preventive strategies. Heat shock protein 70 (HSP70) acts in concert with several cochaperones and nucleotide exchange factors and plays an essential role in protein quality control that increases survival by protecting cells against environmental stressors. Specifically, the HSP70-mediated response has been implicated in the pathogenesis of cancer, but the specific mechanisms by which HSP70 may support malignant cell transformation remains to be fully elucidated. Here, we show that genetic ablation of HSP70 markedly impairs HCC initiation and progression by distinct but overlapping pathways. This includes the potentiation of the carcinogen-induced DNA damage response, at the tumor initiation stage, to increase the p53-dependent surveillance response leading to the cell cycle exit or death of genomically damaged differentiated pericentral hepatocytes, and this may also prevent their conversion into more proliferating HCC progenitor cells. Subsequently, activation of a mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) negative feedback pathway diminishes oncogenic signals, thereby attenuating premalignant cell transformation and tumor progression. Modulation of HSP70 function may be a strategy for interfering with oncogenic signals driving liver cell transformation and tumor progression, thus providing an opportunity for human cancer control.

scholarly journals Mechanism of prostaglandin E2-stimulated heat shock protein 27 induction in osteoblast-like MC3T3-E1 cells

2002 ◽  
Vol 172 (2) ◽  
pp. 271-281 ◽  
Author(s):  
H Tokuda ◽  
O Kozawa ◽  
M Niwa ◽  
H Matsuno ◽  
K Kato ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Prostaglandin E2 ◽  
Map Kinase ◽  
Specific Inhibitor ◽  
Heat Shock Protein 27 ◽  
P38 Map Kinase ◽  
Calphostin C ◽  
Mitogen Activated Protein ◽  
Upstream Kinase

We investigated the effect of prostaglandin E2 (PGE2) on the induction of heat shock protein 27 (HSP27) and HSP70, and the mechanism behind the induction in osteoblast-like MC3T3-E1 cells. PGE2 time-dependently increased the level of HSP27 without affecting the level of HSP70. PGE2 stimulated the accumulation of HSP27 dose-dependently in the range between 10 nM and 10 microM. PGE2 stimulated the increase in the level of the mRNA for HSP27. Staurosporine and calphostin C, inhibitors of protein kinase C (PKC), suppressed the PGE2-induced HSP27 accumulation. The effect of PGE2 on HSP27 accumulation was reduced in the PKC down-regulated cells. BAPTA/AM, a chelator of intracellular Ca2+, or TMB-8, an inhibitor of intracellular Ca2+ mobilization, reduced the accumulation of HSP27 induced by PGE2. Dibutyryl cAMP had little effect on the basal level of HSP27. PGE2 induced the phosphorylation of both p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase. PD98059 and U-0126, inhibitors of the upstream kinase of p44/p42 MAP kinase, reduced the accumulation of HSP27 induced by PGE2. SB203580, a specific inhibitor of p38 MAP kinase, suppressed the HSP27 accumulation induced by PGE2. U-73122, an inhibitor of phospholipase C, and calphostin C reduced the PGE2-induced phosphorylation of both p44/p42 MAP kinase and p38 MAP kinase. These results indicate that PGE2 stimulates the induction of HSP27 through PKC-dependent activations of both p44/p42 MAP kinase and p38 MAP kinase in osteoblasts.

scholarly journals Phosphorylation of the 27-kDa heat shock protein via p38 MAP kinase and MAPKAP kinase in smooth muscle

1997 ◽  
Vol 273 (5) ◽  
pp. L930-L940 ◽  
Author(s):  
Janice K. Larsen ◽  
Ilia A. Yamboliev ◽  
Lee A. Weber ◽  
William T. Gerthoffer
Keyword(s):  
Smooth Muscle ◽  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Map Kinase ◽  
Tyrosine Phosphorylation ◽  
Airway Smooth Muscle ◽  
Muscarinic Receptors ◽  
P38 Map Kinase ◽  
Mitogen Activated Protein

The 27-kDa heat shock protein (HSP27) is expressed in a variety of tissues in the absence of stress and is thought to regulate actin filament dynamics, possibly by a phosphorylation/dephosphorylation mechanism. HSP27 has also been suggested to be involved in contraction of intestinal smooth muscle. We have investigated phosphorylation of HSP27 in airway smooth muscle in response to the muscarinic agonist carbachol. Carbachol increased32P incorporation into canine tracheal HSP27 and induced a shift in the distribution of charge isoforms on two-dimensional gels to more acidic, phosphorylated forms. The canine HSP27 amino acid sequence includes three serine residues corresponding to sites in human HSP27 known to be phosphorylated by mitogen-activated protein kinase-activated protein (MAPKAP) kinase-2. To determine whether muscarinic receptors are coupled to a “stress response” pathway in smooth muscle culminating in phosphorylation of HSP27, we assayed MAPKAP kinase-2 activity and tyrosine phosphorylation of p38 mitogen-activated protein (MAP) kinase, the enzyme thought to activate MAPKAP kinase-2. Recombinant canine HSP27 expressed in Escherichia coli was a substrate for MAPKAP kinase-2 in vitro as well as a substrate for endogenous smooth muscle HSP27 kinase, which was activated by carbachol. Carbachol also increased tyrosine phosphorylation of p38 MAP kinase. SB-203580, an inhibitor of p38 MAP kinases, reduced activation of endogenous HSP27 kinase activity and blocked the shift in HSP27 charge isoforms to acidic forms. We suggest that HSP27 in airway smooth muscle, in addition to being a stress response protein, is phosphorylated by a receptor-initiated signaling cascade involving muscarinic receptors, tyrosine phosphorylation of p38 MAP kinase, and activation of MAPKAP kinase-2.

scholarly journals MAP Kinase Phosphatase-1 Protects against Inflammatory Bone Loss

2009 ◽  
Vol 88 (12) ◽  
pp. 1125-1130 ◽  
Author(s):  
R. Sartori ◽  
F. Li ◽  
K.L. Kirkwood
Keyword(s):  
Bone Loss ◽  
Map Kinase ◽  
Map Kinases ◽  
Group Analysis ◽  
P38 Map Kinase ◽  
Wild Type ◽  
Map Kinase Phosphatase ◽  
Tnf Α ◽  
Protein Map ◽  
Mitogen Activated Protein

The mitogen-activated protein (MAP) kinase phosphatase (MKP) family plays an important function in regulating the pro-inflammatory cytokines by deactivating MAP kinases. MKP-1 is essential for the dephosphorylation of p38 MAP kinase that regulates expression of IL-6, TNF-α, and IL-1β. We hypothesized that MKP-1 regulates inflammatory bone loss in experimental periodontitis. Wild-type and Mkp-1−/− mice received A. actinomycetemcomitans LPS injection in the palatal region or PBS control 3 times/wk for 30 days. Mice were killed, and maxillae were assessed by microcomputed tomography, histological analysis, and TRAP staining for measurement of bone loss, extent of inflammation, and degree of osteoclastogenesis. Results indicated that, in LPS-injected Mkp-1−/− mice, significantly greater bone loss occurred with more inflammatory infiltrate and a significant increase in osteoclastogenesis compared with Mkp-1−/− control sites or either wild-type group. Analysis of these data indicates that MKP-1 plays a key role in the regulation of inflammatory bone loss.

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