scholarly journals Analysis of Mitogen-Activated Protein Kinases in Bone and Cartilage of Patients with Rheumatoid Arthritis Treated with Abatacept

2016 ◽  
Vol 9 ◽  
pp. CMAMD.S34424 ◽  
Author(s):  
Katsuaki Kanbe ◽  
Koei Oh ◽  
Junji Chiba ◽  
Yasuo Inoue ◽  
Masashi Taguchi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Map Kinases ◽  
Histological Changes ◽  
Extracellular Signal ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Hematoxylin And Eosin ◽  
Factor Α ◽  
Necrosis Factor ◽  
And Cartilage

The aim of this study was to analyze the histological changes related to mitogen-activated protein (MAP) kinases in bone and cartilage treated with abatacept for rheumatoid arthritis (RA). A total of 20 patients of bone and cartilage were assessed: 10 abatacept with methotrexate (MTX)-treated RA patients were compared with 10 MTX-treated RA patients (control). The histology of bone and cartilage was observed by staining with hematoxylin and eosin and analyzed immunohistochemically for the expression of tumor necrosis factor-α, interleukin-6, CD4 (T cell), CD68 (macrophage), receptor activator of nuclear kappa-B ligand, osteoprotegerin, osteopontin, CD29 (β-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK (extracellular signal-regulated kinase, ERK1/ERK2), and phosphor-c-Jun N-terminal kinase. The expressions of CD29 known as mechanoreceptor and ERK known as mechanotransduction signal protein in MAP kinases in the bone and cartilage of patients treated with abatacept were significantly different from those of control. These findings suggest that increases in CD29 and ERK in MAP kinases may change the metabolism of bone and cartilage in RA patients treated with abatacept.

scholarly journals Regulation of ERK phosphorylation in differentiated arterial muscle of rabbits

2001 ◽  
Vol 281 (1) ◽  
pp. H114-H123 ◽  
Author(s):  
Paul H. Ratz
Keyword(s):  
Adrenergic Receptor ◽  
Map Kinases ◽  
Mek Inhibitor ◽  
Erk Activation ◽  
Differentiated Cells ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Isolated Arteries

Extracellular signal-regulated kinases (ERK) and mitogen-activated protein (MAP) kinases participate in cell signaling, regulating cell growth. In differentiated cells, the role ERK plays is less well known. This study quantified the degree of basal and stimulated ERK phosphorylation and contraction in freshly isolated arteries. The level of basal ERK phosphorylation was identical in preloaded and slack arteries, was greater in media than in the whole artery, and was reduced by the MAP or ERK kinase (MEK) inhibitor PD-98059. Chemical denudation using 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one did not elevate basal ERK phosphorylation. PD-98059 reduced maximum phenylephrine (PE)-stimulated ERK phosphorylation but not force. Pervanadate elevated ERK phosphorylation without causing contraction. Contractions produced by PE and relaxations produced by PE washout preceded the ERK phosphorylation. K+ depolarization, muscle stretch, and angiotensin II elevated ERK phosphorylation transiently, whereas PE maintained ERK phosphorylation for 30 min. The α1A-adrenergic receptor antagonist WB-4101 reduced PE-stimulated force by 70% and abolished PE-induced ERK phosphorylation. Afterloaded and zero-load contractions produced by K+ depolarization displayed identical increases in ERK phosphorylation. These data indicate that ERK was active basally in the differentiated artery but regulated by the endothelium and that ERK phosphorylation was not load dependent. A strong correlation between PE-induced force and ERK phosphorylation supports the hypothesis that ERK activation may reflect a signal “notifying” the cell of the degree of α1-adrenergic receptor-induced contraction.

scholarly journals Extracellular Signal-regulated Kinase Phosphorylates Tumor Necrosis Factor α-converting Enzyme at Threonine 735: A Potential Role in Regulated Shedding

2002 ◽  
Vol 13 (6) ◽  
pp. 2031-2044 ◽  
Author(s):  
Elena Dı́az-Rodrı́guez ◽  
Juan Carlos Montero ◽  
Azucena Esparı́s-Ogando ◽  
Laura Yuste ◽  
Atanasio Pandiella
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Converting Enzyme ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Factor Α ◽  
Necrosis Factor

The ectodomain of certain transmembrane proteins can be released by the action of cell surface proteases, termed secretases. Here we have investigated how mitogen-activated protein kinases (MAPKs) control the shedding of membrane proteins. We show that extracellular signal-regulated kinase (Erk) acts as an intermediate in protein kinase C-regulated TrkA cleavage. We report that the cytosolic tail of the tumor necrosis factor α-converting enzyme (TACE) is phosphorylated by Erk at threonine 735. In addition, we show that Erk and TACE associate. This association is favored by Erk activation and by the presence of threonine 735. In contrast to the Erk route, the p38 MAPK was able to stimulate TrkA cleavage in cells devoid of TACE activity, indicating that other proteases are also involved in TrkA shedding. These results demonstrate that secretases are able to discriminate between the different stimuli that trigger membrane protein ectodomain cleavage and indicate that phosphorylation by MAPKs may regulate the proteolytic function of membrane secretases.

scholarly journals A Novel Regulatory Mechanism of Map Kinases Activation and Nuclear Translocation Mediated by Pka and the Ptp-Sl Tyrosine Phosphatase

1999 ◽  
Vol 147 (6) ◽  
pp. 1129-1136 ◽  
Author(s):  
Carmen Blanco-Aparicio ◽  
Josema Torres ◽  
Rafael Pulido
Keyword(s):  
Map Kinases ◽  
Nuclear Translocation ◽  
Tyrosine Phosphatase ◽  
Phosphorylation Site ◽  
Extracellular Signal Regulated Kinase ◽  
Inactive Form ◽  
Extracellular Signal ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Dependent Protein

Protein tyrosine phosphatase PTP-SL retains mitogen-activated protein (MAP) kinases in the cytoplasm in an inactive form by association through a kinase interaction motif (KIM) and tyrosine dephosphorylation. The related tyrosine phosphatases PTP-SL and STEP were phosphorylated by the cAMP-dependent protein kinase A (PKA). The PKA phosphorylation site on PTP-SL was identified as the Ser231 residue, located within the KIM. Upon phosphorylation of Ser231, PTP-SL binding and tyrosine dephosphorylation of the MAP kinases extracellular signal–regulated kinase (ERK)1/2 and p38α were impaired. Furthermore, treatment of COS-7 cells with PKA activators, or overexpression of the Cα catalytic subunit of PKA, inhibited the cytoplasmic retention of ERK2 and p38α by wild-type PTP-SL, but not by a PTP-SL S231A mutant. These findings support the existence of a novel mechanism by which PKA may regulate the activation and translocation to the nucleus of MAP kinases.

Phosphatidylinositol 3-kinases regulate ERK and p38 MAP kinases in canine colonic smooth muscle

2000 ◽  
Vol 279 (2) ◽  
pp. C352-C360 ◽  
Author(s):  
Ilia A. Yamboliev ◽  
Kevin M. Wiesmann ◽  
Cherie A. Singer ◽  
Jason C. Hedges ◽  
William T. Gerthoffer
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Map Kinases ◽  
Calf Serum ◽  
Specific Effect ◽  
Kinase C ◽  
Extracellular Signal ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Intact Muscle

In canine colon, M2/M3 muscarinic receptors are coupled to extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinases. We tested the hypothesis that this coupling is mediated by enzymes of the phosphatidylinositol (PI) 3-kinase family. RT-PCR and Western blotting demonstrated expression of two isoforms, PI 3-kinase-α and PI 3-kinase-γ. Muscarinic stimulation of intact muscle strips (10 μM ACh) activated PI 3-kinase-γ, ERK and p38 MAP kinases, and MAP kinase-activated protein kinase-2, whereas PI 3-kinase-α activation was not detected. Wortmannin (25 μM) abolished the activation of PI 3-kinase-γ, ERK, and p38 MAP kinases. MAP kinase inhibition was a PI 3-kinase-γ-specific effect, since wortmannin did not inhibit recombinant activated murine ERK2 MAP kinase, protein kinase C, Raf-1, or MAP kinase kinase. In cultured muscle cells, newborn calf serum (3%) activated PI 3-kinase-α and PI 3-kinase-γ isoforms, ERK and p38 MAP kinases, and stimulated chemotactic cell migration. Using wortmannin and LY-294002 to inhibit PI 3-kinase activity and PD-098059 and SB-203580 to inhibit ERK and p38 MAP kinases, we established that these enzymes are functionally important for regulation of chemotactic migration of colonic myocytes.

scholarly journals The Tumor Suppressor p53 Inhibits Net, an Effector of Ras/Extracellular Signal-Regulated Kinase Signaling

2004 ◽  
Vol 24 (3) ◽  
pp. 1132-1142 ◽  
Author(s):  
Koji Nakade ◽  
Hong Zheng ◽  
Gitali Ganguli ◽  
Gilles Buchwalter ◽  
Christian Gross ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Suppressor ◽  
Map Kinases ◽  
Specific Gene ◽  
Tumor Suppressor P53 ◽  
Extracellular Signal ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Map Kinase Pathway

ABSTRACT The tumor suppressor function of p53 is linked to its ability to repress gene expression, but the mechanisms of specific gene repression are poorly understood. We report that wild-type p53 inhibits an effector of the Ras oncogene/mitogen-activated protein (MAP) kinase pathway, the transcription factor Net. Tumor-associated mutant p53s are less efficient inhibitors. p53 inhibits by preventing phosphorylation of Net by MAP kinases. Loss of p53 in vivo leads to increased Net phosphorylation in response to wound healing and UV irradiation of skin. Our results show that p53 can repress specific gene expression by inhibiting Net, a factor implicated in cell cycle entry.

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