MAP Kinase Upstream Kinase

ABSTRACTAdaptation to a changing environment is essential for the survival and propagation of sessile organisms, such as plants or fungi. Filamentous fungi commonly respond to a worsening of their growth conditions by differentiation of asexually or sexually produced spores. The formation of these specialized cell types is, however, also triggered as part of the general life cycle by hyphal age or density. Spores typically serve for dispersal and, therefore, translocation but can also act as resting states to endure times of scarcity. Eukaryotic differentiation in response to environmental and self-derived signals is commonly mediated by three-tiered mitogen-activated protein (MAP) kinase signaling cascades. Here, we report that the MAP kinase Fus3 of the black moldAspergillus niger(AngFus3) and its upstream kinase AngSte7 control vegetative spore formation and secondary metabolism. Mutants lacking these kinases are defective in conidium induction in response to hyphal density but are fully competent in starvation-induced sporulation, indicating that conidiation inA. nigeris triggered by various independent signals. In addition, the mutants exhibit an altered profile of volatile metabolites and secrete dark pigments into the growth medium, suggesting a dysregulation of the secondary metabolism. By assigning the AngFus3 MAP kinase pathway to the transduction of a potentially self-derived trigger, this work contributes to the unraveling of the intricate signaling networks controlling fungal differentiation. Moreover, our data further support earlier observations that differentiation and secondary metabolism are tightly linked in filamentous fungi.

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

Journal of Endocrinology ◽

10.1677/joe.0.1720271 ◽

2002 ◽

Vol 172 (2) ◽

pp. 271-281 ◽

Cited By ~ 19

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.

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

Blood ◽

10.1182/blood.v90.3.929.929_929_934 ◽

1997 ◽

Vol 90 (3) ◽

pp. 929-934 ◽

Cited By ~ 6

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.

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Mitogen-activated protein kinase translocates to the nucleus during ischaemia and is activated during reperfusion

Biochemical Journal ◽

10.1042/bj3230785 ◽

1997 ◽

Vol 323 (3) ◽

pp. 785-790 ◽

Cited By ~ 47

Author(s):

Yoichi MIZUKAMI ◽

Ken-ichi YOSHIDA

Keyword(s):

Map Kinase ◽

Tyrosine Phosphorylation ◽

Mitogen Activated Protein Kinase ◽

Nuclear Fraction ◽

Cytosol Fraction ◽

Extracellular Signal ◽

Ischaemia And Reperfusion ◽

Mitogen Activated Protein ◽

Upstream Kinase ◽

Cellular Stresses

Growth factors and various cellular stresses are known to activate mitogen-activated protein (MAP) kinase, which plays a role in conveying signals from the cytosol to the nucleus. The phosphorylation of MAP kinase is thought to be a prerequisite for translocation. Here, we investigate the translocation and activation of MAP kinase during ischaemia and reperfusion in perfused rat heart. Ischaemia (0–40 min) induces the translocation of MAP kinase from the cytosol fraction to the nuclear fraction. Immunohistochemical observation shows that MAP kinase staining in the nucleus is enhanced after ischaemia for 40 min. Unexpectedly, tyrosine phosphorylation of MAP kinase is unchanged in the nuclear fraction during ischaemia, indicating that unphosphorylated MAP kinase translocates from the cytosol to the nucleus. During reperfusion (0–30 min), after ischaemia for 20 min, tyrosine phosphorylation of MAP kinase in the nuclear fraction is increased with a peak at 10 min of reperfusion. The activation is confirmed by MAP kinase activity with similar kinetics to the tyrosine phosphorylation. However, the amount of MAP kinase in the fraction is almost constant during reperfusion for 10 min. Although an upstream kinase for MAP kinase, MAP kinase/extracellular signal-regulated kinase kinase (MEK)-1, remains in the cytosol throughout ischaemia and reperfusion, MEK-2, another upstream kinase for MAP kinase, is constantly present in the nucleus as well as in the cytoplasm, based on analyses by fractionation and immunohistochemistry. Furthermore, MEK-2 activity in the nuclear fraction is rapidly increased during post-ischaemic reperfusion. These findings demonstrate that nuclear MAP kinase is activated by tyrosine phosphorylation during reperfusion, probably by MEK-2.

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MAP Kinase Upstream Kinase

Encyclopedia of Signaling Molecules ◽

10.1007/978-3-319-67199-4_102153 ◽

2018 ◽

pp. 2934-2934

Keyword(s):

Map Kinase ◽

Upstream Kinase

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

Blood ◽

10.1182/blood.v90.3.929 ◽

1997 ◽

Vol 90 (3) ◽

pp. 929-934 ◽

Cited By ~ 63

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.

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p38 MAP kinase regulates BMP-4-stimulated VEGF synthesis via p70 S6 kinase in osteoblasts

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00300.2002 ◽

2003 ◽

Vol 284 (6) ◽

pp. E1202-E1209 ◽

Cited By ~ 30

Author(s):

Haruhiko Tokuda ◽

Daijiro Hatakeyama ◽

Toshiyuki Shibata ◽

Shigeru Akamatsu ◽

Yutaka Oiso ◽

...

Keyword(s):

Map Kinase ◽

Map Kinases ◽

Kinase Inhibitor ◽

Mammalian Target Of Rapamycin ◽

Negative Control ◽

P38 Map Kinase ◽

S6 Kinase ◽

P70 S6 Kinase ◽

Upstream Kinase ◽

Sb 203580

We previously reported that p70 S6 kinase takes part in bone morphogenetic protein-4 (BMP-4)-stimulated vascular endothelial growth factor (VEGF) synthesis in osteoblast-like MC3T3-E1 cells. Recently, we showed that BMP-4-induced osteocalcin synthesis is regulated by p44/p42 MAP kinase and p38 MAP kinase in these cells. In the present study, we investigated whether the MAP kinases are involved in the BMP-4-stimulated synthesis of VEGF in MC3T3-E1 cells. PD-98059 and U-0126, inhibitors of the upstream kinase of p44/p42 MAP kinase, failed to affect BMP-4-stimulated VEGF synthesis. SB-203580 and PD-169316, inhibitors of p38 MAP kinase, significantly reduced VEGF synthesis, whereas SB-202474, a negative control for p38 MAP kinase inhibitor, had little effect on VEGF synthesis. The BMP-4-stimulated phosphorylation of p38 MAP kinase was not affected by rapamycin, an inhibitor of p70 S6 kinase. On the contrary, SB-203580 and PD-169316 reduced the BMP-4-stimulated phosphorylation of p70 S6 kinase. In addition, anisomycin, an activator of p38 MAP kinase, phosphorylates p70 S6 kinase, and the phosphorylation was suppressed by SB-203580. LY-294002, an inhibitor of phosphatidylinositol 3-kinase, failed to suppress the phosphorylation of p38 MAP kinase induced by BMP-4. Not BMP-4 but anisomycin weakly induced the phosphorylation of phosphoinositide-dependent kinase-1. However, anisomycin had little effect on phosphorylation of either Akt or the mammalian target of rapamycin. Taken together, our results suggest that p38 MAP kinase functions in BMP-4-stimulated VEGF synthesis as a positive regulator at a point upstream from p70 S6 kinase in osteoblasts.

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