Extracellular signal-regulated kinase pathway is differentially involved in β-agonist-induced hypertrophy in slow and fast muscles

2007 ◽  
Vol 292 (5) ◽  
pp. C1681-C1689 ◽  
Author(s):  
H. Shi ◽  
C. Zeng ◽  
A. Ricome ◽  
K. M. Hannon ◽  
A. L. Grant ◽  
...  
Keyword(s):  
Fiber Type ◽  
Erk Signaling ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Erk Activity ◽  
Fast Muscles ◽  
Slow And Fast Muscles

The molecular mechanisms controlling β-adrenergic receptor agonist (BA)-induced skeletal muscle hypertrophy are not well known. We presently report that BA exerts a distinct muscle- and muscle fiber type-specific hypertrophy. Moreover, we have shown that pharmacologically or genetically attenuating extracellular signal-regulated kinase (ERK) signaling in muscle fibers resulted in decreases ( P < 0.05) in fast but not slow fiber type-specific reporter gene expressions in response to BA exposure in vitro and in vivo. Consistent with these data, forced expression of MAPK phosphatase 1, a nuclear protein that dephosphorylates ERK1/2, in fast-twitch skeletal muscle ablated ( P < 0.05) the hypertrophic effects of BA feeding (clenbuterol, 20 parts per million in water) in vivo. Further analysis has shown that BA-induced phosphorylation and activation of ERK occurred to a greater ( P < 0.05) extent in fast myofibers than in slow myofibers. Analysis of the basal level of ERK activity in slow and fast muscles revealed that ERK1/2 is activated to a greater extent in fast- than in slow-twitch muscles. These data indicate that ERK signaling is differentially involved in BA-induced hypertrophy in slow and fast skeletal muscles, suggesting that the increased abundance of phospho-ERK1/2 and ERK activity found in fast-twitch myofibers, compared with their slow-twitch counterparts, may account, at least in part, for the fiber type-specific hypertrophy induced by BA stimulation. These data suggest that fast myofibers are pivotal in the adaptation of muscle to environmental cues and that the mechanism underlying this change is partially mediated by the MAPK signaling cascade.

scholarly journals Effect of thyroid hormone on the myosin heavy chain isoforms in slow and fast muscles of the rat.

1999 ◽  
Vol 46 (3) ◽  
pp. 823-835 ◽  
Author(s):  
A Jakubiec-Puka ◽  
I Ciechomska ◽  
U Mackiewicz ◽  
J Langford ◽  
H Chomontowska
Keyword(s):  
Thyroid Hormone ◽  
Myosin Heavy Chain ◽  
Soleus Muscle ◽  
Heavy Chain ◽  
Myosin Heavy Chain Isoforms ◽  
Leg Muscles ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Fast Muscles ◽  
Slow And Fast Muscles

The myosin heavy chain (MHC) was studied by biochemical methods in the slow-twitch (soleus) and two fast-twitch leg muscles of the triiodothyronine treated (hyperthyroid), thyroidectomized (hypothyroid) and euthyroid (control) rats. The changes in the contents of individual MHC isoforms(MHC-1, MHC-2A, MHC-2B and MHC-2X) were evaluated in relation to the muscle mass and the total MHC content. The MHC-1 content decreased in hyperthyreosis, while it increased in hypothyreosis in the soleus and in the fast muscles. The MHC-2A content increased in hyperthyreosis and it decreased in hypothyreosis in the soleus muscle. In the fast muscles hyperthyreosis did not affect the MHC-2A content, whereas hypothyreosis caused an increase in this MHC isoform content. The MHC-2X, present only in traces or undetected in the control soleus muscle, was synthesised in considerable amount in hyperthyreosis; in hypothyreosis the MHC-2X was not detected in the soleus. In the fast muscles the content of MHC-2X was not affected by any changes in the thyroid hormone level. The MHC-2B seemed to be not influenced by hyperthyreosis in the fast muscles, whereas the hypothyreosis caused a decrease of its content. In the soleus muscle the MHC-2B was not detected in any groups of rats. The results suggest that the amount of each of the four MHC isoforms expressed in the mature rat leg muscles is influenced by the thyroid hormone in a different way. The MHC-2A and the MHC-2X are differently regulated in the soleus and in the fast muscles; thyroid hormone seems to be necessary for expression of those isoforms in the soleus muscle.

In vivo Ca2+ buffering capacity and microvascular oxygen pressures following muscle contractions in diabetic rat skeletal muscles: fiber-type specific effects

2015 ◽  
Vol 309 (2) ◽  
pp. R128-R137 ◽  
Author(s):  
Hiroaki Eshima ◽  
David C. Poole ◽  
Yutaka Kano
Keyword(s):  
Fiber Type ◽  
Recovery Period ◽  
Muscle Contractions ◽  
Diabetic Rat ◽  
Type I ◽  
Type Ii ◽  
Protein Levels ◽  
Slow Twitch ◽  
Fast Twitch

In Type 1 diabetes, skeletal muscle resting intracellular Ca2+ concentration ([Ca2+]i) homeostasis is impaired following muscle contractions. It is unclear to what degree this behavior is contingent upon fiber type and muscle oxygenation conditions. We tested the hypotheses that: 1) the rise in resting [Ca2+]i evident in diabetic rat slow-twitch (type I) muscle would be exacerbated in fast-twitch (type II) muscle following contraction; and 2) these elevated [Ca2+]i levels would relate to derangement of microvascular partial pressure of oxygen (PmvO2) rather than sarcoplasmic reticulum dysfunction per se. Adult male Wistar rats were divided randomly into diabetic (DIA: streptozotocin ip) and healthy (CONT) groups. Four weeks later extensor digitorum longus (EDL, predominately type II fibers) and soleus (SOL, predominately type I fibers) muscle contractions were elicited by continuous electrical stimulation (120 s, 100 Hz). Ca2+ imaging was achieved using fura 2-AM in vivo (i.e., circulation intact). DIA increased fatigability in EDL ( P < 0.05) but not SOL. In recovery, SOL [Ca2+]i either returned to its resting baseline within 150 s (CONT 1.00 ± 0.02 at 600 s) or was not elevated in recovery at all (DIA 1.03 ± 0.02 at 600 s, P > 0.05). In recovery, EDL CONT [Ca2+]i also decreased to values not different from baseline (1.06 ± 0.01, P > 0.05) at 600 s. In marked contrast, EDL DIA [Ca2+]i remained elevated for the entire recovery period (i.e., 1.23 ± 0.03 at 600 s, P < 0.05). The inability of [Ca2+]i to return to baseline in EDL DIA was not associated with any reduction of SR Ca2+-ATPase (SERCA) 1 or SERCA2 protein levels (both increased 30–40%, P < 0.05). However, PmvO2 recovery kinetics were markedly slowed in EDL such that mean PmvO2 was substantially depressed (CONT 27.9 ± 2.0 vs. DIA 18.4 ± 2.0 Torr, P < 0.05), and this behavior was associated with the elevated [Ca2+]i. In contrast, this was not the case for SOL ( P > 0.05) in that neither [Ca2+]i nor PmvO2 were deranged in recovery with DIA. In conclusion, recovery of [Ca2+]i homeostasis is impaired in diabetic rat fast-twitch but not slow-twitch muscle in concert with reduced PmvO2 pressures.

scholarly journals Divergent Dynamics and Functions of ERK MAP Kinase Signaling in Development, Homeostasis and Cancer: Lessons from Fluorescent Bioimaging

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 513 ◽  
Author(s):  
Yu Muta ◽  
Michiyuki Matsuda ◽  
Masamichi Imajo
Keyword(s):  
Cell Fate ◽  
Cellular Responses ◽  
Erk Signaling ◽  
Biological Processes ◽  
Cell Level ◽  
Erk Activation ◽  
Cell Fate Decisions ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Erk Activity

The extracellular signal-regulated kinase (ERK) signaling pathway regulates a variety of biological processes including cell proliferation, survival, and differentiation. Since ERK activation promotes proliferation of many types of cells, its deregulated/constitutive activation is among general mechanisms for cancer. Recent advances in bioimaging techniques have enabled to visualize ERK activity in real-time at the single-cell level. Emerging evidence from such approaches suggests unexpectedly complex spatiotemporal dynamics of ERK activity in living cells and animals and their crucial roles in determining cellular responses. In this review, we discuss how ERK activity dynamics are regulated and how they affect biological processes including cell fate decisions, cell migration, embryonic development, tissue homeostasis, and tumorigenesis.

scholarly journals Signal Pathways Which Promote Invasion and Metastasis: Critical and Distinct Contributions of Extracellular Signal-Regulated Kinase and Ral-Specific Guanine Exchange Factor Pathways

2001 ◽  
Vol 21 (17) ◽  
pp. 5958-5969 ◽  
Author(s):  
Yvona Ward ◽  
Warner Wang ◽  
Elisa Woodhouse ◽  
Ilona Linnoila ◽  
Lance Liotta ◽  
...  
Keyword(s):  
Dominant Negative ◽  
Signal Pathways ◽  
Nucleotide Exchange ◽  
3T3 Cells ◽  
Invasion And Metastasis ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Erk Activity

ABSTRACT Approximately 50% of metastatic tumors contain Ras mutations. Ras proteins can activate at least three downstream signaling cascades mediated by the Raf–MEK–extracellular signal-regulated kinase family, phosphatidylinositol-3 (PI3) kinase, and Ral-specific guanine nucleotide exchange factors (RalGEFs). Here we investigated the contribution of RalGEF and ERK activation to the development of experimental metastasis in vivo and associated invasive properties in vitro. Each pathway contributes distinct properties to the metastatic phenotype. Following lateral tail vein injection, 3T3 cells transformed by constitutively active Raf or MEK produced lung metastasis that displayed circumscribed, noninfiltrating borders. In contrast, 3T3 cells transformed by Ras(12V,37G), a Ras effector mutant that activates RalGEF but not Raf or P13 kinase, formed aggressive, infiltrative metastasis. Dominant negative RalB inhibited Ras(12V,37G)-activated invasion and metastasis, demonstrating the necessity of the RalGEF pathway for a fully transformed phenotype. Moreover, 3T3 cells constitutively expressing a membrane-associated form of RalGEF (RalGDS-CAAX) formed invasive tumors as well, demonstrating that activation of a RalGEF pathway is sufficient to initiate the invasive phenotype. Despite the fact that Ras(12V,37G) expression does not elevate ERK activity, inhibition of this kinase by a conditionally expressed ERK phosphatase demonstrated that ERK activity was necessary for Ras(12V,37G)-transformed cells to express matrix-degrading activity in vitro and tissue invasiveness in vivo. Therefore, these experiments have revealed a hitherto-unknown but essential interaction of the RalGEF and ERK pathways to produce a malignant phenotype. The generality of the role of the RalGEF pathway in metastasis is supported by the finding that Ras(12V,37G) increased the invasiveness of epithelial cells as well as fibroblasts.

scholarly journals Intercellular propagation of extracellular signal-regulated kinase activation revealed by in vivo imaging of mouse skin

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Toru Hiratsuka ◽  
Yoshihisa Fujita ◽  
Honda Naoki ◽  
Kazuhiro Aoki ◽  
Yuji Kamioka ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Mouse Skin ◽  
Egf Receptors ◽  
M Cell ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Erk Activity

Extracellular signal-regulated kinase (ERK) is a key effector of many growth signalling pathways. In this study, we visualise epidermal ERK activity in living mice using an ERK FRET biosensor. Under steady-state conditions, the epidermis occasionally revealed bursts of ERK activation patterns where ERK activity radially propagated from cell to cell. The frequency of this spatial propagation of radial ERK activity distribution (SPREAD) correlated with the rate of epidermal cell division. SPREADs and proliferation were stimulated by 12-O-tetradecanoylphorbol 13-acetate (TPA) in a manner dependent on EGF receptors and their cognate ligands. At the wounded skin, ERK activation propagated as trigger wave in parallel to the wound edge, suggesting that ERK activation propagation can be superimposed. Furthermore, by visualising the cell cycle, we found that SPREADs were associated with G2/M cell cycle progression. Our results provide new insights into how cell proliferation and transient ERK activity are synchronised in a living tissue.

scholarly journals Inhibition of gonadotropin-stimulated steroidogenesis by the erk cascade

2019 ◽  
Author(s):  
Rony Seger ◽  
Tamar Hanoch ◽  
Revital Rosenberg ◽  
Ada Dantes ◽  
Wolfgang E. Merz ◽  
...  
Keyword(s):  
Protein A ◽  
Erk Signaling ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Progesterone Production ◽  
Extracellular Signal ◽  
Progesterone Synthesis ◽  
Steroidogenic Acute Regulatory ◽  
Erk Activity ◽  
Stimulation Of

LH and FSH are two important hormones in the regulation of granulosa cells. Their effects are mediated mainly by cAMP/PKA signaling, bit the activity of the extracellular signal-regulated kinase (ERK) signaling cascade is elevated as well. We studied the involvement of the ERK cascade in LH and FSH-induced steroidogenesis in two granulosa-derived cell lines, rLHR-4 and rFSHR-17, respectively. We found that stimulation of these cells with the appropriate gonadotropin induced ERK activation as well as progesterone production, downstream of PKA. Inhibition of ERK activity enhanced gonadotropin-stimulated progesterone production, which was correlated with increased-expression of the steroidogenic acute regulatory (StAR) protein, a key regulator of progesterone synthesis. Therefore, it is likely that gonadotropin-stimulated progesterone formation is regulated by a pathway that includes PKA and StAR, and this process is downregulated by ERK, due to attenuation of StAR expression. Our results suggest that activation of PKA signaling by gonadotropins not only induces steroidogenesis, but also activates downregulation machinery involving the ERK cascade. The activation of ERK by gonadotropins as well as by other agents, may be a key mechanism for the modulation of gonadotropin-induced steroidogenesis.

scholarly journals Extracellular Signal-Regulated Kinase (ERK) Activity During Sleep Consolidates Cortical Plasticity In Vivo

2013 ◽  
Vol 25 (2) ◽  
pp. 507-515 ◽  
Author(s):  
Michelle C. Dumoulin ◽  
Sara J. Aton ◽  
Adam J. Watson ◽  
Leslie Renouard ◽  
Tammi Coleman ◽  
...  
Keyword(s):  
Cortical Plasticity ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Erk Activity

scholarly journals Dual-specificity phosphatase 5 controls the localized inhibition, propagation, and transforming potential of ERK signaling

2017 ◽  
Vol 114 (3) ◽  
pp. E317-E326 ◽  
Author(s):  
Andrew M. Kidger ◽  
Linda K. Rushworth ◽  
Julia Stellzig ◽  
Jane Davidson ◽  
Christopher J. Bryant ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Fate ◽  
Erk Signaling ◽  
Feedback Mechanisms ◽  
Extracellular Signal Regulated Kinase ◽  
Raf Kinase ◽  
Dual Specificity ◽  
Extracellular Signal ◽  
A Cell ◽  
Erk Activity

Deregulated extracellular signal-regulated kinase (ERK) signaling drives cancer growth. Normally, ERK activity is self-limiting by the rapid inactivation of upstream kinases and delayed induction of dual-specificity MAP kinase phosphatases (MKPs/DUSPs). However, interactions between these feedback mechanisms are unclear. Here we show that, although the MKP DUSP5 both inactivates and anchors ERK in the nucleus, it paradoxically increases and prolongs cytoplasmic ERK activity. The latter effect is caused, at least in part, by the relief of ERK-mediated RAF inhibition. The importance of this spatiotemporal interaction between these distinct feedback mechanisms is illustrated by the fact that expression of oncogenic BRAFV600E, a feedback-insensitive mutant RAF kinase, reprograms DUSP5 into a cell-wide ERK inhibitor that facilitates cell proliferation and transformation. In contrast, DUSP5 deletion causes BRAFV600E-induced ERK hyperactivation and cellular senescence. Thus, feedback interactions within the ERK pathway can regulate cell proliferation and transformation, and suggest oncogene-specific roles for DUSP5 in controlling ERK signaling and cell fate.

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