Filamin associates with stress signalling kinases MKK7 and MKK4 and regulates JNK activation

Nakagawa, Kentaro; Sugahara, Misato; Yamasaki, Tokiwa; Kajiho, Hiroaki; Takahashi, Shinya; Hirayama, Jun; Minami, Yasuhiro; Ohta, Yasutaka; Watanabe, Toshio; Hata, Yoshinobu; Katada, Toshiaki; Nishina, Hiroshi

doi:10.1042/bj20091011

Cited by 27 publications

(23 citation statements)

References 22 publications

(44 reference statements)

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“…Sun et al (23) reported that MEKK4 could stimulate JNK and p38 activation in the human prostate adenocarcinoma cell line after tumor necrosis factor-related apoptosis-inducing ligand treatment, which might contribute to cell apoptosis. Nakagawa et al (19) reported MKK4 and MKK7 sequentially phosphorylated tyrosine and threonine residues of JNK, respectively, and phosphorylation of both residues would lead to synergistic JNK activation in stress-stimulated embryonic stem cells, which might play an important role in stress signaling. However, to our knowledge, no data about the role of MEKK4, MKK4, or MKK7 in TGF-␤1 expression were reported previously.…”

Section: Discussionmentioning

confidence: 98%

JNK-dependent AP-1 activation is required for aristolochic acid-induced TGF-β1 synthesis in human renal proximal epithelial cells

Rui

Wang

Cheng

et al. 2012

American Journal of Physiology-Renal Physiology

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Chronic aristolochic acid nephropathy (CAAN) is a chronic and progressive tubulointerstitial nephropathy characterized by extensive interstitial fibrosis. Aristolochic acid (AA) could induce overexpression of transforming growth factor-β1 (TGF-β1) in a human renal proximal tubule epithelial cells line (HKC), which has been implicated in the pathogenesis of CAAN. The present studies in HKC cells showed 1) AA could activate JNK in time- and dose-dependent manners and JNK inhibitor SP600125 could inhibit AA-induced TGF-β1 promoter activity and TGF-β1 synthesis; 2) AA-induced JNK activation and TGF-β1 synthesis were significantly inhibited by kinase-inactive mutants of MEKK4, MKK4, or MKK7; 3) AA could upregulate luciferase activity derived by a wild-type TGF-β1 promoter, but not by an AP-1 binding-deficient TGF-β1 promoter; and 4) AA could upregulate expression of c-Fos, phospho-c-Jun, and phospho-ATF2. The above data suggest AA-induced TGF-β1 overexpression in HKC cells may be mainly mediated by the JNK signaling pathway. Both the upstream kinases of JNK including MEKK4, MKK4, and MKK7, and the downstream transcription factor of JNK, AP-1, may also participate in this process.

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Section: Discussionmentioning

confidence: 98%

JNK-dependent AP-1 activation is required for aristolochic acid-induced TGF-β1 synthesis in human renal proximal epithelial cells

Rui

Wang

Cheng

et al. 2012

American Journal of Physiology-Renal Physiology

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“…Although only one substrate, Rab1, was studied in depth in this study, a number of these substrates fit with known characteristics of TAK1 signaling. Filamin A functions as a scaffold for MKK4 and JNK association and activation of JNK (41,42). MKK4 is a direct substrate of TAK1, thus it is possible TAK1 also associates with Filamin A to stimulate MKK4/JNK signaling.…”

Section: Discussionmentioning

confidence: 99%

Innate immunity kinase TAK1 phosphorylates Rab1 on a hotspot for posttranslational modifications by host and pathogen

Levin

Hertz

Burlingame

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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TGF-β activated kinase 1 (TAK1) is a critical signaling hub responsible for translating antigen binding signals to immune receptors for the activation of the AP-1 and NF-κB master transcriptional programs. Despite its importance, known substrates of TAK1 are limited to kinases of the MAPK and IKK families and include no direct effectors of biochemical processes. Here, we identify over 200 substrates of TAK1 using a chemical genetic kinase strategy. We validate phosphorylation of the dynamic switch II region of GTPase Rab1, a mediator of endoplasmic reticulum to Golgi vesicular transport, at T75 to be regulated by TAK1 in vivo. TAK1 preferentially phosphorylates the inactive (GDP-bound) state of Rab1. Phosphorylation of Rab1 disrupts interaction with GDP dissociation inhibitor 1 (GDI1), but not guanine exchange factor (GEF) or GTPaseactivating protein (GAP) enzymes, and is exclusive to membranelocalized Rab1, suggesting phosphorylation may stimulate Rab1 membrane association. Furthermore, we found phosphorylation of Rab1 at T75 to be essential for Rab1 function. Previous studies established that the pathogen Legionella pneumophila is capable of hijacking Rab1 function through posttranslational modifications of the switch II region. Here, we present evidence that Rab1 is regulated by the host in a similar fashion, and that the innate immunity kinase TAK1 and Legionella effectors compete to regulate Rab1 by switch II modifications during infection.

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“…For example, phosphorylation of myosin light chain kinase (MLCK) and filamin by MAPK has been reported, as has an effect of phosphorylation on their activity and subsequent cytoskeletal reorganization (He et al, 2003;Nakagawa et al, 2010;Kim and McCulloch, 2011). As discussed above, filamin has been identified in a complex with ␤-arrestins and ERK1/2.…”

Section: ␤-Arrestin-scaffolded Mapks and Cytoskeletal Reorganizationmentioning

confidence: 99%

β-Arrestin-Dependent Actin Reorganization: Bringing the Right Players Together at the Leading Edge

Min¹,

DeFea²

2011

Mol Pharmacol

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First identified as mediators of G-protein-coupled receptor desensitization and internalization and later as signaling platforms, ␤-arrestins play a requisite role in chemotaxis and reorganization of the actin cytoskeleton, downstream of multiple receptors. However, the precise molecular mechanisms underlying their involvement have remained elusive. Initial interest in ␤-arrestins as facilitators of cell migration and actin reorganization stemmed from the known interplay between receptor endocytosis and actin filament formation, because disruption of the actin cytoskeleton inhibits these ␤-arrestin-dependent events. With growing interest in the mechanisms by which cells can sense a gradient of agonist during cell migration, investigators began to hypothesize that ␤-arrestins may contribute to directed migration by controlling chemotactic receptor turnover at the plasma membrane. Finally, increasing evidence emerged that ␤-arrestins are more than just clathrin adaptor proteins involved in turning off receptor signals; they are actually capable of generating their own signals by scaffolding signaling molecules and controlling the activity of multiple cellular enzymes. This new role of ␤-arrestins as signaling scaffolds has led to the hypothesis that they can facilitate cell migration by sequestering actin assembly activities and upstream regulators of actin assembly at the leading edge. This Minireview discusses recent advances in our understanding of how ␤-arrestin scaffolds contribute to cell migration, focusing on recently identified ␤-arrestin interacting proteins and phosphorylation targets that have known roles in actin reorganization.

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Filamin associates with stress signalling kinases MKK7 and MKK4 and regulates JNK activation

Cited by 27 publications

References 22 publications

JNK-dependent AP-1 activation is required for aristolochic acid-induced TGF-β1 synthesis in human renal proximal epithelial cells

JNK-dependent AP-1 activation is required for aristolochic acid-induced TGF-β1 synthesis in human renal proximal epithelial cells

Innate immunity kinase TAK1 phosphorylates Rab1 on a hotspot for posttranslational modifications by host and pathogen

β-Arrestin-Dependent Actin Reorganization: Bringing the Right Players Together at the Leading Edge

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