scholarly journals Hematopoietic Protein Tyrosine Phosphatase Mediates β2-Adrenergic Receptor-Induced Regulation of p38 Mitogen-Activated Protein Kinase in B Lymphocytes

2008 ◽  
Vol 29 (3) ◽  
pp. 675-686 ◽  
Author(s):  
Jaclyn W. McAlees ◽  
Virginia M. Sanders
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Protein Tyrosine Phosphatase ◽  
Adrenergic Receptor ◽  
Tyrosine Phosphatase ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Mapk Activation ◽  
Mapk Phosphorylation ◽  
Mitogen Activated Protein

ABSTRACT Stimulation of the β2-adrenergic receptor (β2AR) on a CD40L/interleukin-4-activated B lymphocyte increases the level of immunoglobulin E (IgE) in a protein kinase A (PKA)- and p38 mitogen-activated protein kinase (MAPK)-dependent manner. However, the mechanism by which β2AR stimulation mediates the increase in the level of p38 MAPK activation has remained unclear. Here we show that the β2AR-induced increase in p38 MAPK activation occurred via a hematopoietic protein tyrosine phosphatase (HePTP)-mediated cross talk between PKA and p38 MAPK. β2AR agonists, cAMP-elevating agents, and PKA inhibitors were used to show that β2AR stimulation resulted in a PKA-dependent increase in p38 MAPK phosphorylation. Pharmacological agents and gene-deficient mice revealed that p38 MAPK phosphorylation was regulated by the G-stimulatory (Gs)/cAMP/PKA pathway independently of the G-inhibitory or β-arrestin-2 pathways. Coimmunoprecipitation and Western blot analysis showed that HePTP was phosphorylated in a PKA-dependent manner, which inactivated HePTP and allowed for increased free p38 MAPK to be phosphorylated by the MAPK cascade that was activated by CD40L. HePTP short hairpin RNA confirmed that HePTP played a role in regulating the level of p38 MAPK phosphorylation in a B cell. Thus, β2AR stimulation on a B cell phosphorylates and inactivates HePTP in a Gs/cAMP/PKA-dependent manner to release bound p38 MAPK, making more available for phosphorylation and subsequent IgE regulation.

scholarly journals APPL1 mediates adiponectin-stimulated p38 MAPK activation by scaffolding the TAK1-MKK3-p38 MAPK pathway

2011 ◽  
Vol 300 (1) ◽  
pp. E103-E110 ◽  
Author(s):  
Xiaoban Xin ◽  
Lijun Zhou ◽  
Caleb M. Reyes ◽  
Feng Liu ◽  
Lily Q. Dong
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Adaptor Protein ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Scaffolding Protein ◽  
Mapk Activation ◽  
P38 Mapk Pathway ◽  
Mitogen Activated Protein

The adaptor protein APPL1 mediates the stimulatory effect of adiponectin on p38 mitogen-activated protein kinase (MAPK) signaling, yet the underlying mechanism remains unclear. Here we show that, in C2C12 cells, overexpression or suppression of APPL1 enhanced or suppressed, respectively, adiponectin-stimulated p38 MAPK upstream kinase cascade, consisting of transforming growth factor-β-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase 3 (MKK3). In vitro affinity binding and coimmunoprecipitation experiments revealed that TAK1 and MKK3 bind to different regions of APPL1, suggesting that APPL1 functions as a scaffolding protein to facilitate adiponectin-stimulated p38 MAPK activation. Interestingly, suppressing APPL1 had no effect on TNFα-stimulated p38 MAPK phosphorylation in C2C12 myotubes, indicating that the stimulatory effect of APPL1 on p38 MAPK activation is selective. Taken together, our study demonstrated that the TAK1-MKK3 cascade mediates adiponectin signaling and uncovers a scaffolding role of APPL1 in regulating the TAK1-MKK3-p38 MAPK pathway, specifically in response to adiponectin stimulation.

scholarly journals The TGFβ-induced phosphorylation and activation of p38 mitogen-activated protein kinase is mediated by MAP3K4 and MAP3K10 but not TAK1

Open Biology ◽  
2013 ◽  
Vol 3 (6) ◽  
pp. 130067 ◽  
Author(s):  
Gopal P. Sapkota
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Phosphorylation ◽  
Mesenchymal Transition ◽  
Mitogen Activated Protein

The signalling pathways downstream of the transforming growth factor beta (TGFβ) family of cytokines play critical roles in all aspects of cellular homeostasis. The phosphorylation and activation of p38 mitogen-activated protein kinase (MAPK) has been implicated in TGFβ-induced epithelial-to-mesenchymal transition and apoptosis. The precise molecular mechanisms by which TGFβ cytokines induce the phosphorylation and activation of p38 MAPK are unclear. In this study, I demonstrate that TGFβ-activated kinase 1 (TAK1/MAP3K7) does not play a role in the TGFβ-induced phosphorylation and activation of p38 MAPK in MEFs and HaCaT keratinocytes. Instead, RNAi -mediated depletion of MAP3K4 and MAP3K10 results in the inhibition of the TGFβ-induced p38 MAPK phosphorylation. Furthermore, the depletion of MAP3K10 from cells homozygously knocked-in with a catalytically inactive mutant of MAP3K4 completely abolishes the TGFβ-induced phosphorylation of p38 MAPK, implying that among MAP3Ks, MAP3K4 and MAP3K10 are sufficient for mediating the TGFβ-induced activation of p38 MAPK.

scholarly journals hVH-5: A Protein Tyrosine Phosphatase Abundant in Brain that Inactivates Mitogen-Activated Protein Kinase

2002 ◽  
Vol 65 (4) ◽  
pp. 1823-1833 ◽  
Author(s):  
Karen J. Martell ◽  
Audrey F. Seasholtz ◽  
Seung P. Kwak ◽  
Kristina K. Clemens ◽  
Jack E. Dixon
Keyword(s):  
Protein Kinase ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Mitogen Activated Protein Kinase ◽  
Protein Tyrosine ◽  
Mitogen Activated Protein

scholarly journals p38 Mitogen-Activated Protein Kinase/Hog1p Regulates Translation of the AU-Rich-Element-Bearing MFA2 Transcript

2005 ◽  
Vol 25 (22) ◽  
pp. 9753-9763 ◽  
Author(s):  
Shobha Vasudevan ◽  
Nicole Garneau ◽  
Danny Tu Khounh ◽  
Stuart W. Peltz
Keyword(s):  
Protein Kinase ◽  
Carbon Source ◽  
P38 Mapk ◽  
Growth Conditions ◽  
Mitogen Activated Protein Kinase ◽  
Stability Factor ◽  
Translation Efficiency ◽  
Dependent Manner ◽  
Translation Repression ◽  
Mitogen Activated Protein

ABSTRACT AU-rich-element (ARE)-mediated mRNA regulation occurs in Saccharomyces cerevisiae in response to external and internal stimuli through the p38 mitogen-activated protein kinase (MAPK)/Hog1p pathway. We demonstrate that the ARE-bearing MFA2 3′ untranslated region (UTR) controls translation efficiency in a p38 MAPK/Hog1p-dependent manner in response to carbon source growth conditions. The carbon source-regulated effect on MFA2 3′-UTR-controlled translation involves the role of conserved ARE binding proteins, the ELAV/TIA-1-like Pub1p, which can interact with the cap/eIF4G complex, and the translation/mRNA stability factor poly(A) binding protein (Pab1p). Pub1p binds the MFA2 3′-UTR in a p38 MAPK/Hog1p-regulated manner in response to carbon source growth conditions. Significantly, the p38 MAPK/Hog1p is also required to modulate Pab1p in response to carbon source. We find that Pab1p can bind the MFA2 3′-UTR in a regulated manner to control MFA2 3′-UTR reporter translation. Binding of full-length Pab1p to the MFA2 3′-UTR correlates with translation repression. Importantly, Pab1p binds the MFA2 3′-UTR only in a PUB1 strain, and correlating with this requirement, Pub1p controls translation repression of MFA2 in a carbon source/Hog1p-regulated manner. These results suggest that the p38 MAPK/Hog1p pathway regulates 3′-UTR-mediated translation by modulating recruitment of Pab1p and Pub1p, which can interact with the translation machinery.

Prior exercise increases basal and insulin-induced p38 mitogen-activated protein kinase phosphorylation in human skeletal muscle

2003 ◽  
Vol 94 (6) ◽  
pp. 2337-2341 ◽  
Author(s):  
Farah S. L. Thong ◽  
Wim Derave ◽  
Birgitte Ursø ◽  
Bente Kiens ◽  
Erik A. Richter
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
P38 Mapk ◽  
Human Skeletal Muscle ◽  
Insulin Infusion ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Phosphorylation ◽  
Prior Exercise ◽  
Mitogen Activated Protein

We have examined the effects of insulin on p38 mitogen-activated protein kinase (MAPK) phosphorylation in human skeletal muscle and the effects of prior exercise hereon. Seven men performed 1-h one-legged knee extensor exercise 3 h before the initiation of a 100-min euglycemic-hyperinsulinemic (600 pmol/l) clamp. Glucose uptake across the legs was measured with the leg balance technique, and muscle biopsies were obtained from the rested and exercised vastus lateralis before and during insulin infusion. Net glucose uptake during the clamp was ∼50% higher ( P< 0.05) in the exercised leg than in the rested leg. Insulin induced a modest sustained 1.2- and 1.3-fold increase ( P < 0.05) in p38 MAPK phosphorylation in the rested and exercised legs, respectively. However, p38 phosphorylation was ∼50% higher ( P < 0.05) in the exercised compared with the rested leg before and during insulin infusion. We conclude that a physiological concentration of insulin causes modest but sustained activation of the p38 MAPK pathway in human skeletal muscle. Furthermore, the stimulatory effect of exercise on p38 phosphorylation is persistent for at least 3 h after exercise and remains evident during subsequent insulin stimulation. Because p38 MAPK has been suggested to play a necessary role in activation of GLUT-4 at the cell surface, the present data may suggest a putative role of p38 MAPK in the increased insulin sensitivity of skeletal muscle after exercise.

scholarly journals Effects of ethanol on mitogen-activated protein kinase and stress-activated protein kinase cascades in normal and regenerating liver

1998 ◽  
Vol 334 (3) ◽  
pp. 669-676 ◽  
Author(s):  
Jianping CHEN ◽  
Edward J. N. ISHAC ◽  
Paul DENT ◽  
George KUNOS ◽  
Bin GAO
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Ethanol Exposure ◽  
Selective Inhibitor ◽  
Chronic Ethanol ◽  
Mitogen Activated Protein Kinase ◽  
Hepatocyte Proliferation ◽  
Mapk Activation ◽  
Chronic Ethanol Consumption ◽  
Mitogen Activated Protein

To understand the mechanisms by which ethanol inhibits hepatocyte proliferation, we studied the effects of ethanol on p42/44 mitogen-activated protein kinase (MAPK), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) in normal and regenerating rat liver. Treatment of rat hepatocytes with 100 mM ethanol in vitro for 16 h prolonged the activation of p42/44 MAPK and p38 MAPK induced by various agonists. Such treatment also increased basal JNK activity, but did not potentiate or prolong agonist-induced JNK activation. Ethanol potentiation of the activation of p42/44 MAPK was abolished by pertussis toxin. In contrast, chronic ethanol consumption in vivo inhibited the activation of p42/44 MAPK, p38 MAPK and JNK induced either by partial hepatectomy or by various agonists. However, both acute and chronic ethanol inhibited hepatocyte proliferation induced by insulin and epidermal growth factor. A selective inhibitor of p42/44 MAPK partially prevented the inhibition of hepatocyte proliferation caused by acute, but not by chronic, ethanol exposure, whereas a selective inhibitor of p38 MAPK further inhibited hepatocyte proliferation under both conditions. These data suggest that acute and chronic ethanol inhibit hepatocyte proliferation by different mechanisms. The effect of acute ethanol may be related to the prolongation of p42/44 MAPK activation, whereas inhibition of hepatocyte proliferation by chronic ethanol may be due to inhibition of p38 MAPK activation.

Insulin inhibits PDGF-directed VSMC migration via NO/ cGMP increase of MKP-1 and its inactivation of MAPKs

2002 ◽  
Vol 283 (3) ◽  
pp. C704-C713 ◽  
Author(s):  
Asha Jacob ◽  
Jeffery D. Molkentin ◽  
Albert Smolenski ◽  
Suzanne M. Lohmann ◽  
Najma Begum
Keyword(s):  
Protein Kinase ◽  
Inhibitory Effect ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Mapk Phosphorylation ◽  
Adenoviral Infection ◽  
Cgmp Signaling ◽  
Mitogen Activated Protein ◽  
And Migration ◽  
Insulin Inhibition

In this study, we examined the role of insulin in the control of vascular smooth muscle cell (VSMC) migration in the normal vasculature. Platelet-derived growth factor (PDGF) increased VSMC migration, which was inhibited by pretreatment with insulin in a dose-dependent manner. Insulin also caused a 60% decrease in PDGF-stimulated mitogen-activated protein kinase (MAPK) phosphorylation and activation. Insulin inhibition of MAPK was accompanied by a rapid induction of MAPK phosphatase (MKP-1), which inactivates MAPKs by dephosphorylation. Pretreatment with inhibitors of the nitric oxide (NO)/cGMP pathway, blocked insulin-induced MKP-1 expression and restored PDGF-stimulated MAPK activation and migration. In contrast, adenoviral infection of VSMCs with MKP-1 or cGMP-dependent protein kinase Iα (cGK Iα), the downstream effector of cGMP signaling, blocked the activation of MAPK and prevented PDGF-directed VSMC migration. Expression of antisense MKP-1 RNA prevented insulin's inhibitory effect and restored PDGF-directed VSMC migration and MAPK phosphorylation. We conclude that insulin inhibition of VSMC migration may be mediated in part by NO/cGMP/cGK Iα induction of MKP-1 and consequent inactivation of MAPKs.

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