Retraction: Corrigendum: Leishmania-Specific Promiscuous Membrane Protein Tubulin Folding Cofactor D Divulges Th1/Th2 Polarization in the Host via ERK-1/2 and p38 MAPK Signaling Cascade

We have previously demonstrated that transforming growth factor-β1 (TGF-β1) rapidly activates the mitogen-activated protein kinase kinase 3 (MKK3)-p38 MAPK signaling cascade, leading to the induction of type I collagen synthesis in mouse glomerular mesangial cells (Wang L, Ma R, Flavell RA, Choi ME. J Biol Chem 277: 47257–47262, 2002). In the present study, we investigated the functional role of upstream TGF-β-activated kinase 1 (TAK1) and TAK1-binding protein 1 (TAB1) in the TGF-β1 signaling cascade. Rapid activation of endogenous TAK1 activity by TGF-β1 was observed in mouse mesangial cells. Transient overexpression of TAK1 with TAB1 enhanced the activation of MKK3 and p38 MAPK with or without TGF-β1 stimulation, whereas a dominant-negative mutant of TAK1 (TAK1DN) suppressed TGF-β1-induced activation of MKK3 and p38 MAPK. Moreover, constitutive expression of TAK1DN reduced steady-state protein levels of MKK3 and p38 MAPK as well as MKK3 phosphorylation. Increased p38α MAPK activity by ectopic expression of either TAB1 or wild-type p38α MAPK resulted in enhanced TGF-β1-induced type I collagen expression. In contrast, constitutive expression of TAK1DN inhibited collagen induction. Taken together, our data indicate that TAK1 and TAB1 play a pivotal role as upstream signal transducers activating the MKK3-p38 MAPK signaling cascade that leads to the induction of type I collagen expression by TGF-β1. In addition, our findings also suggest that TAK1 has a novel function in regulation of the steady-state protein levels of MKK3 and p38 MAPK.

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Synthesis, characterization and in vitro and in vivo photodynamic activities of a gallium(iii) tris(ethoxycarbonyl)corrole

Dalton Transactions ◽

10.1039/c7dt00992e ◽

2017 ◽

Vol 46 (29) ◽

pp. 9481-9490 ◽

Cited By ~ 21

Author(s):

Zhao Zhang ◽

Hua-Hua Wang ◽

Hua-Jun Yu ◽

Yu-Zhen Xiong ◽

Hai-Tao Zhang ◽

...

Keyword(s):

Cancer Cells ◽

P38 Mapk ◽

Mapk Signaling ◽

Signaling Cascade ◽

Highly Effective

A gallium(iii) tris(ethoxycarbonyl)corrole is a highly effective photosensitizer against A549 cancer cells via p38 MAPK signaling cascade pathways.

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Acquisition of Letrozole Resistance Through Activation of the p38/MAPK Signaling Cascade

Anticancer Research ◽

10.21873/anticanres.14810 ◽

2021 ◽

Vol 41 (2) ◽

pp. 583-599

Author(s):

RASHIDRA R. WALKER ◽

KAREN M. GALLEGOS ◽

MELYSSA R. BRATTON ◽

KITANI P. LEMIEUX ◽

KUN ZHANG ◽

...

Keyword(s):

P38 Mapk ◽

Mapk Signaling ◽

Signaling Cascade

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Involvement of the p38 MAPK signaling cascade in stress response of RAW 264.7 macrophages

Doklady Biological Sciences ◽

10.1134/s0012496617050015 ◽

2017 ◽

Vol 476 (1) ◽

pp. 203-205 ◽

Cited By ~ 3

Author(s):

E. G. Novoselova ◽

O. V. Glushkova ◽

M. O. Khrenov ◽

S. B. Parfenyuk ◽

S. M. Lunin ◽

...

Keyword(s):

Stress Response ◽

P38 Mapk ◽

Mapk Signaling ◽

Signaling Cascade ◽

Raw 264.7 ◽

Raw 264.7 Macrophages

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Bag3 P209L myopathies and efficacy of blocking signaling pathways with the therapeutic peptide, MMI-0100

Proceedings of IMPRS ◽

10.18060/23478 ◽

2019 ◽

Vol 2 (1) ◽

Author(s):

Ashley R. Hacker ◽

Jessica M. Berthiaume ◽

Monte S. Willis

Keyword(s):

P38 Mapk ◽

Cardiac Dysfunction ◽

Systolic Function ◽

Critical Role ◽

Mapk Signaling ◽

Signaling Cascade ◽

Littermate Control ◽

Cellular Processes ◽

Established Disease ◽

First Time

Background and Hypothesis: The Bcl2-associated anthanogene (BAG) 3 protein is a member of the BAG family of cochaperones, which play a critical role in cellular processes, including protein degradation and turnover. Over 30 Bag3 mutations have been identified, including a Proline209Leucine (P209L) missense mutation which causes a severe childhood cardiomyopathy. The mechanism by which Bag3 mutations causes cardiomyopathy is currently unknown, but the p38/MAPK signaling cascade has been shown to be altered in our animal model that coexpresses the human Bag3 P209L gene. We hypothesized the cell-permeant peptide, MMI-0100, which is known to inhibit MAPK-activated protein kinase 2 (MK2) activity in the p38/MAPK signaling cascade, would alleviate or reduce cardiac dysfunction. Experimental Design: Echocardiographic analysis of cardiac function of cardiac-specific Bag3 P209L transgenic (and wildtype littermate control) mice (20 – 22 months of age) was assessed by high-resolution ultrasound echocardiography (VisualSonics Vevo 2100, MS550D probe, cardiology package) to document the established disease-related cardiac dysfunction at baseline. Mice were then treated with 100mg/kg/day MMI-0100 nebulized daily for 30 days. Follow-up echocardiography was performed at 10, 20, and 30 days of MMI-0100 treatment. Echocardiographic analysis was performed to determine the systolic function (EF%, FS%), chamber dimensions, and wall thickness in systole and diastole using Vevo 2100 Workstation software package. Results: Blinded analysis of echocardiographic data identified that Bag3 P209L Tg+ mice had a baseline cardiac dysfunction compared to wildtype controls at 20 months of age (WT= 76% EF, 44% FS; Tg+= 66% EF, 36% FS). MMI-0100 treatment significantly attenuated this dysfunction by 20 days of MMI-0100 treatment (WT= 79% EF, 47% FS; Tg+= 80% EF, 48% FS), consistent with demonstrating for the first time MK2’s role in mediating p38 signaling in the pathogenesis of Bag3 P209L cardiomyopathy. Conclusion and Potential Impact: The MMI-0100 peptide has proven efficacious in several animal models of fibrosis driven by p38 signaling, as MK2 is a p38 downstream mediator. Future studies seek to translate the use of the MMI-0100 peptide in pediatric patients with Bag3 P209L cardiomyopathy through compassionate use FDA pathways.

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An evolutionarily conserved Rit GTPase–p38 MAPK signaling pathway mediates oxidative stress resistance

Molecular Biology of the Cell ◽

10.1091/mbc.e11-05-0400 ◽

2011 ◽

Vol 22 (17) ◽

pp. 3231-3241 ◽

Cited By ~ 37

Author(s):

Weikang Cai ◽

Jennifer L. Rudolph ◽

Susan M. W. Harrison ◽

Ling Jin ◽

Aubrey L. Frantz ◽

...

Keyword(s):

Oxidative Stress ◽

P38 Mapk ◽

Knockout Mice ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Signaling Cascade ◽

Mapk Cascades ◽

Wide Range ◽

Evolutionarily Conserved ◽

Stress Dependent

Ras-related small GTP-binding proteins control a wide range of cellular processes by regulating a variety of effector pathways, including prominent roles in the control of mitogen-activated protein kinase (MAPK) cascades. Although the regulatory role(s) for many Ras family GTPases are well established, the physiological function for the Rit/Rin subfamily has been lacking. Here, using both knockout mice and Drosophila models, we demonstrate an evolutionarily conserved role for Rit subfamily GTPases (mammalian Rit and Rin, and the Drosophila RIC homologue) in governing survival in response to oxidative stress. Primary embryonic fibroblasts derived from Rit knockout mice display increased apoptosis and selective disruption of MAPK signaling following reactive oxygen species (ROS) exposure but not in response to endoplasmic reticulum stress or DNA damage. These deficits include a reduction in ROS-mediated stimulation of a p38-MK2-HSP27 signaling cascade that controls Akt activation, directing Bad phosphorylation to promote cell survival. Furthermore, D-RIC null flies display increased susceptibility to environmental stresses and reduced stress-dependent p38 signaling, extending the Rit-p38 survival pathway to Drosophila. Together, our studies establish the Rit GTPases as critical regulators of an evolutionarily conserved, p38 MAPK–dependent signaling cascade that functions as an important survival mechanism for cells in response to oxidative stress.

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