scholarly journals Activation of p38 MAP Kinase Pathway by Erythropoietin and Interleukin-3

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 929-934 ◽  
Author(s):  
Yuka Nagata ◽  
Tetsuo Moriguchi ◽  
Eisuke Nishida ◽  
Kazuo Todokoro
Keyword(s):  
Map Kinase ◽  
Osmotic Shock ◽  
Interleukin 1 ◽  
P38 Map Kinase ◽  
Kinase Assay ◽  
Upstream Kinase ◽  
In Vitro Kinase Assay ◽  
Map Kinase Pathway ◽  
Factor Α

Activation of p38 MAP kinase (p38) as well as JNK/SAPK has been described as being induced by a variety of environmental stresses such as osmotic shock, ultraviolet radiation, and heat shock, or the proinflammatory cytokines tumor necrosis factor-α and interleukin-1 (IL-3). We found that the hematopoietic cytokines erythropoietin (Epo) and IL-3, which regulate growth and differentiation of erythroids and hematopoietic progenitors, respectively, also activate a p38 cascade. Immunoblot analyses and in vitro kinase assay clearly showed that Epo and IL-3 rapidly and transiently phosphorylated and activated p38 in Epo– or IL-3–dependent mouse hematopoietic progenitor cells. p38 can generally be activated by the upstream kinase MKK3 or MKK6. However, in vitro kinase assays in the immunoprecipitates with anti-MKK6 antibody and anti-phosphorylated MKK3/MKK6 antibody showed that activation of neither MKK3 nor MKK6 was detected after Epo or IL-3 stimulation, while osmotic shock clearly induced activation of both MKK3/MKK6 and p38. Together with previous observations, these results suggest that both p38 and JNK cascades play an important role not only in stress and proinflammatory cytokine responses but also in hematopoietic cytokine actions.

scholarly journals Activation of p38 MAP Kinase Pathway by Erythropoietin and Interleukin-3

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 929-934 ◽  
Author(s):  
Yuka Nagata ◽  
Tetsuo Moriguchi ◽  
Eisuke Nishida ◽  
Kazuo Todokoro
Keyword(s):  
Map Kinase ◽  
Osmotic Shock ◽  
Interleukin 1 ◽  
P38 Map Kinase ◽  
Kinase Assay ◽  
Upstream Kinase ◽  
In Vitro Kinase Assay ◽  
Map Kinase Pathway ◽  
Factor Α

Abstract Activation of p38 MAP kinase (p38) as well as JNK/SAPK has been described as being induced by a variety of environmental stresses such as osmotic shock, ultraviolet radiation, and heat shock, or the proinflammatory cytokines tumor necrosis factor-α and interleukin-1 (IL-3). We found that the hematopoietic cytokines erythropoietin (Epo) and IL-3, which regulate growth and differentiation of erythroids and hematopoietic progenitors, respectively, also activate a p38 cascade. Immunoblot analyses and in vitro kinase assay clearly showed that Epo and IL-3 rapidly and transiently phosphorylated and activated p38 in Epo– or IL-3–dependent mouse hematopoietic progenitor cells. p38 can generally be activated by the upstream kinase MKK3 or MKK6. However, in vitro kinase assays in the immunoprecipitates with anti-MKK6 antibody and anti-phosphorylated MKK3/MKK6 antibody showed that activation of neither MKK3 nor MKK6 was detected after Epo or IL-3 stimulation, while osmotic shock clearly induced activation of both MKK3/MKK6 and p38. Together with previous observations, these results suggest that both p38 and JNK cascades play an important role not only in stress and proinflammatory cytokine responses but also in hematopoietic cytokine actions.

scholarly journals Twitchin kinase interacts with MAPKAP kinase 2 in Caenorhabditis elegans striated muscle

2015 ◽  
Vol 26 (11) ◽  
pp. 2096-2111 ◽  
Author(s):  
Yohei Matsunaga ◽  
Hiroshi Qadota ◽  
Miho Furukawa ◽  
Heejoo (Helen) Choe ◽  
Guy M. Benian
Keyword(s):  
Caenorhabditis Elegans ◽  
Map Kinase ◽  
Striated Muscle ◽  
P38 Map Kinase ◽  
Dynamics Simulation ◽  
Catalytic Core ◽  
C Elegans ◽  
Map Kinase Pathway ◽  
Pulling Force

In Caenorhabditis elegans, twitchin is a giant polypeptide located in muscle A-bands. The protein kinase of twitchin is autoinhibited by 45 residues upstream (NL) and 60 residues downstream (CRD) of the kinase catalytic core. Molecular dynamics simulation on a twitchin fragment revealed that the NL is released by pulling force. However, it is unclear how the CRD is removed. To identify proteins that may remove the CRD, we performed a yeast two-hybrid screen using twitchin kinase as bait. One interactor is MAK-1, C. elegans orthologue of MAPKAP kinase 2. MAPKAP kinase 2 is phosphorylated and activated by p38 MAP kinase. We demonstrate that the CRD of twitchin is important for binding to MAK-1. mak-1 is expressed in nematode body wall muscle, and antibodies to MAK-1 localize between and around Z-disk analogues and to the edge of A-bands. Whereas unc-22 mutants are completely resistant, mak-1 mutants are partially resistant to nicotine. MAK-1 can phosphorylate twitchin NL-Kin-CRD in vitro. Genetic data suggest the involvement of two other mak-1 paralogues and two orthologues of p38 MAP kinase. These results suggest that MAK-1 is an activator of twitchin kinase and that the p38 MAP kinase pathway may be involved in the regulation of twitchin.

Thioredoxin Negatively Regulates p38 MAP Kinase Activation and IL-6 Production by Tumor Necrosis Factor-α

1999 ◽  
Vol 258 (2) ◽  
pp. 443-447 ◽  
Author(s):  
Shu Hashimoto ◽  
Ken Matsumoto ◽  
Yasuhiro Gon ◽  
Sachiko Furuichi ◽  
Shuichiro Maruoka ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Map Kinase ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
P38 Map Kinase ◽  
Kinase Activation ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals The MADD-3 LAMMER Kinase Interacts with a p38 MAP Kinase Pathway to Regulate the Display of the EVA-1 Guidance Receptor in Caenorhabditis elegans

PLoS Genetics ◽  
2016 ◽  
Vol 12 (4) ◽  
pp. e1006010 ◽  
Author(s):  
Serena A. D’Souza ◽  
Luckshi Rajendran ◽  
Rachel Bagg ◽  
Louis Barbier ◽  
Derek M. van Pel ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Caenorhabditis Elegans ◽  
Map Kinase ◽  
Motor Neurons ◽  
Leading Edge ◽  
P38 Map Kinase ◽  
Endosomal Trafficking ◽  
Guidance Cue ◽  
Map Kinase Pathway ◽  
Kinase Pathway

The proper display of transmembrane receptors on the leading edge of migrating cells and cell extensions is essential for their response to guidance cues. We previously discovered that MADD-4, which is an ADAMTSL secreted by motor neurons in Caenorhabditis elegans, interacts with an UNC-40/EVA-1 co-receptor complex on muscles to attract plasma membrane extensions called muscle arms. In nematodes, the muscle arm termini harbor the post-synaptic elements of the neuromuscular junction. Through a forward genetic screen for mutants with disrupted muscle arm extension, we discovered that a LAMMER kinase, which we call MADD-3, is required for the proper display of the EVA-1 receptor on the muscle’s plasma membrane. Without MADD-3, EVA-1 levels decrease concomitantly with a reduction of the late-endosomal marker RAB-7. Through a genetic suppressor screen, we found that the levels of EVA-1 and RAB-7 can be restored in madd-3 mutants by eliminating the function of a p38 MAP kinase pathway. We also found that EVA-1 and RAB-7 will accumulate in madd-3 mutants upon disrupting CUP-5, which is a mucolipin ortholog required for proper lysosome function. Together, our data suggests that the MADD-3 LAMMER kinase antagonizes the p38-mediated endosomal trafficking of EVA-1 to the lysosome. In this way, MADD-3 ensures that sufficient levels of EVA-1 are present to guide muscle arm extension towards the source of the MADD-4 guidance cue.

Boswellia serrata oleo-gum-resin and β-boswellic acid inhibits HSV-1 infection in vitro through modulation of NF-кB and p38 MAP kinase signaling

Phytomedicine ◽  
2018 ◽  
Vol 51 ◽  
pp. 94-103 ◽  
Author(s):  
Debayan Goswami ◽  
Ananya Das Mahapatra ◽  
Subhadip Banerjee ◽  
Amit Kar ◽  
Durbadal Ojha ◽  
...  
Keyword(s):  
Map Kinase ◽  
P38 Map Kinase ◽  
Kinase Signaling ◽  
Boswellic Acid ◽  
Boswellia Serrata ◽  
Map Kinase Signaling ◽  
Hsv 1

scholarly journals Differential role of cAMP, cGMP and Ca2+ and involvement of kinases and CBP-CREB-CRE pathway in regulation of arylalkylamine N-acetyltransferase 2 gene in the pineal organ of air-breathing catfish, Clarias gariepinus

2021 ◽  
Author(s):  
Hijam Nonibala ◽  
Braj Bansh Prasad Gupta
Keyword(s):  
Gene Expression ◽  
Map Kinase ◽  
Gene Transcription ◽  
Pineal Organ ◽  
Clarias Gariepinus ◽  
Specific Inhibitor ◽  
P38 Map Kinase ◽  
Camp And Cgmp

Abstract Transcription of arylalkylamine N-acetyltransferase 2 (aanat2) gene leads to formation of AANAT2 - the rate-limiting enzyme in melatonin synthesis pathway in photosensitive fish pineal organ. However, unlike in avian and mammalian pineal gland, there is practically no information on signal transduction pathway(s) involved in regulation of aanat2 gene transcription in the fish pineal organ. Therefore, we investigated the role of important molecular components of signalling via cAMP, cGMP, Ca2+ involving PKA, PKG, PKC, MeK and p38 MAP kinase as well as possible role of serine/threonine phosphatases, CREB and CBP using their specific inhibitors and/or activators in aanat2 gene transcription in the fish pineal organ maintained under in vitro culture-conditions. db-cAMP and db-cGMP stimulated the expression of aanat2 gene. db-cAMP- and cGMP-induced aanat2 gene expression was significantly reduced in the presence of H-89 (specific inhibitor of PKA), KT5823 (specific inhibitor of PKG), chelerythrine chloride (specific inhibitor of PKC), U0126 ethanolate (specific inhibitor of MeK) and SB 202190 monohydrochloride hydrate (specific inhibitor of p38 MAP kinase). Inhibitors of PP1 and PP2A significantly increased aanat2 gene expression as well as significantly reduced cAMP- and cGMP-induced gene transcription, while inhibitor of PP2B had no effect on aanat2 gene expression. Inhibitors of both CREB and CBP-CREB interaction completely blocked cAMP-induced aanat2 gene transcription. Based on these findings, we suggest that cAMP, cGMP and Ca2+ stimulate aanat2 gene transcription via PKA, PKG and PKC, respectively. Further, protein phosphatases and CBP-CREB-CRE pathway are actively involved in regulation of on aanat2 gene expression in the fish pineal organ.

The Augmented Productions of Neopterin and Cytokines from Macrophages/monocytes in vitro

Pteridines ◽  
1996 ◽  
Vol 7 (3) ◽  
pp. 72-76
Author(s):  
Tadashi Lizuka ◽  
Mitsuyo Sasaki ◽  
Hitomi Kamisako ◽  
Ko Oishi ◽  
Shigeru Uemura ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Interleukin 1 ◽  
Poly I:C ◽  
Recombinant Interferon ◽  
Preliminary Examination ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α ◽  
Necrosis Factor

Summary In Kawasaki disease patients, increases in excretion of urinary neopterin coincided with fever and monocytosis in peripheral blood. We examined the products of neopterin, tumor necrosis factor-α (TNFα) and Interleukin-1 β (1L-1β) from healthy adult macrophages/monocytes (Mφ>/M), after stimulation with several activators to obtain some understanding of Kawasaki disease. Upon stimulation with either lipopolysaccharide (LPS) or polyinosinate-polycytidylate (Poly I:C), the Mφ/M released neopterin and pyogenic products (TNF-α or 1L-1β). The release of neopterin was eliminated by the addition of the anti-interferon-y antibody. The production of both TNF-α, 1L-1β and neopterin from Mφ/M upon stimulation of LPS was augmented in a co-culture with low dose recombinant interferon-y (rIFN-γ). Upon stimulation with rIFN-γ alone, however, the Mφ/M released neopterin but not the pyogenic products. A preliminary examination failed to detect. any difference in the response of the Mφ/M in adults annd children after stimulation with LPS. We concluded that some endotoxins could trigger the onset of Kawasaki disease and that endogenous IFN-γ can play an important role in the abnormality of Kawasaki disease patients

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