Targeted disruption of the Tab1 gene causes embryonic lethality and defects in cardiovascular and lung morphogenesis

Komatsu, Yoshihiro; Shibuya, H.; Takeda, Nobuo; Ninomiya‐Tsuji, Jun; Yasui, Takeshi; Miyado, Kenji; Sekimoto, Tomohisa; Ueno, Naoto; Matsumoto, Kunihiro; Yamada, Gen

doi:10.1016/s0925-4773(02)00391-x

Cited by 88 publications

(69 citation statements)

References 60 publications

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“…After E10.5, the embryonic structures were resorbed in the Tak1 mutants. Interestingly, the mutant phenotype of Tak1 embryos is substantially different from Tab1 (abnormal cardiovascular and pulmonary morphogenesis) and Tab2 (liver degeneration and apoptosis) mutant embryos (Table 2; Komatsu et al 2002;Sanjo et al 2003). The phenotypes of the mutant embryos suggest that the TAK1 complex does not only function as a single unit but, instead, that each component has a distinct role during development.…”

Section: Abnormal Development Of Neural Tube In Tak1 Mutant Embryosmentioning

confidence: 92%

“…However, the physiological roles of mammalian TAK1, TAB1, and TAB2 in inflammatory signaling in vivo remain to be definitively established. TAB1-deficient mouse embryonic fibroblasts (MEFs) have been generated; however, TAB1 function has not been tested in TNFR1 and IL-1R/TLRmediated signaling (Komatsu et al 2002). Surprisingly, TAB2-deficient MEFs are capable of activating IKK and JNK normally in response to TNF-␣ or IL-1 (Sanjo et al 2003).…”

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confidence: 99%

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TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo

Shim¹,

Xiao²,

Paschal³

et al. 2005

Genes Dev.

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657

628

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Section: Abnormal Development Of Neural Tube In Tak1 Mutant Embryosmentioning

confidence: 92%

mentioning

confidence: 99%

TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo

Shim¹,

Xiao²,

Paschal³

et al. 2005

Genes Dev.

Self Cite

657

628

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show abstract

“…These results reinforce earlier experiments showing that RNAi and chemical inhibitors of TAK1 blocked IKK and JNK activation by multiple pathways . In contrast to TAK1, deletion of TAB1 or TAB2 did not affect NF-kB activation by IL-1b or TNFa (Komatsu et al, 2002;Sanjo et al, 2003). As biochemical experiments had shown that TAB1 is dispensable for IKK activation by TRAF6 in vitro (Wang et al, 2001), it is likely that TAB1 is involved in other signalling pathways (e.g., TGF-b) instead of the NFkB pathway.…”

Section: The Traf Family Of Ubiquitin-protein Ligases (E3)mentioning

confidence: 94%

Ubiquitin-mediated activation of TAK1 and IKK

2007

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Transforming growth factor b activated kinase-1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase family, has emerged as a key regulator of signal transduction cascades leading to the activation of the transcription factors nuclear factor-kappa B (NF-jB) and activator protein-1 (AP-1). Stimulation of cells with cytokines and microbial pathogens results in the activation of TAK1, which subsequently activates the I-kappa B kinase complex (IKK) and mitogen-activated protein (MAP) kinases, culminating in the activation of NF-jB and AP-1, respectively. Recent studies have shown that polyubiquitination of signalling proteins through lysine (Lys)-63-linked polyubiquitin chains plays an important role in the activation of TAK1 and IKK. Unlike Lys-48-linked polyubiquitination, which normally targets proteins for degradation by the proteasome, Lys-63-linked polyubiquitin chains act as scaffolds to assemble protein kinase complexes and mediate their activation through proteasome-independent mechanisms. The concept of ubiquitin-mediated activation of protein kinases is supported by the discoveries of ubiquitination and deubiquitination enzymes as well as ubiquitin-binding proteins that function upstream of TAK1 and IKK. Recent biochemical and genetic studies provide further insights into the mechanism and function of ubiquitin signalling and these advances will be the focus of this review.

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“…Further studies are required to determine the physiological context of TAB1-mediated p38 MAPK activation. Importantly, the recent description of Tab1 −/− mice, which die during early embryogenesis with cardiovascular and lung dysmorphogenesis, will facilitate this analysis (Komatsu et al 2002).…”

Section: Activation Of P38 Map Kinase By Mapkk-independent Mechanismsmentioning

confidence: 99%

Mechanism of p38 MAP kinase activation in vivo

Brancho¹,

Tanaka²,

Jaeschke³

et al. 2003

Genes Dev.

450

403

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The p38 mitogen-activated protein kinase (MAPK) is activated in vitro by three different protein kinases: MKK3, MKK4, and MKK6. To examine the relative roles of these protein kinases in the mechanism of p38 MAP kinase activation in vivo, we examined the effect of disruption of the murine Mkk3, Mkk4, and Mkk6 genes on the p38 MAPK signaling pathway. We show that MKK3 and MKK6 are essential for tumor necrosis factor-stimulated p38 MAPK activation. In contrast, ultraviolet radiation-stimulated p38 MAPK activation was mediated by MKK3, MKK4, and MKK6. Loss of p38 MAPK activation in the mutant cells was associated with defects in growth arrest and increased tumorigenesis. These data indicate that p38 MAPK is regulated by the coordinated and selective actions of three different protein kinases in response to cytokines and exposure to environmental stress. Several groups of mitogen-activated protein kinase (MAPK) signal transduction pathways have been identified in mammals, including extracellular signal-regulated protein kinase (ERK), c-Jun NH 2 -terminal kinase (JNK), and p38 MAPK. Each of these groups of MAPK is activated by dual phosphorylation on Thr and Tyr within a tripeptide motif (Thr-Xaa-Tyr) located within the activation loop of the MAPK. This phosphorylation is mediated by seven MAPK kinases (MAPKKs) that have specificity for individual MAPK isoforms. Thus, ERK1 and ERK2 are activated by MEK1 and MEK2, ERK5 is activated by MEK5, JNK is activated by MKK4 and MKK7, and p38 MAPK is activated by MKK3 and MKK6 (Schaeffer and Weber 1999; Kyriakis and Avruch 2001). These MAPKKs and MAPKs can create independent signaling modules that may function in parallel.The mechanism that accounts for the specificity of MAPKKs to activate individual MAPK isoforms is mediated, in part, by an interaction between an N-terminal region located on the MAPKK and a docking site located on the MAPK (Bardwell and Thorner 1996; Enslen and Davis 2001). Recently, structural insight into the mechanism of interaction between a MAPKK and a MAPK has been achieved by X-ray crystallography (Chang et al. 2002). This analysis demonstrated that there is a direct interaction of the N-terminal region of the MAPKK with a docking groove present on the surface of the MAPK distant from the catalytic active site (Weston et al. 2002). A second determinant of MAPKK specificity is the structure of the MAPK activation loop that contains the ThrXaa-Tyr dual phosphorylation motif (Enslen et al. 2000). The specificity of these interactions mediate, in part, the ability of an individual MAPKK to activate a particular MAPK selectively.It is interesting that mammalian MAPK signaling modules include more than one MAPKK because in yeast only a single MAPKK appears to activate each MAPK. The role of this pathway complexity in mammals is unclear. However, it may be significant that individual yeast MAPK isoforms are activated by only a limited group of extracellular stimuli, but mammalian MAPK isoforms are activated by a wide array of extracellular stimuli. It is there...

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Targeted disruption of the Tab1 gene causes embryonic lethality and defects in cardiovascular and lung morphogenesis

Cited by 88 publications

References 60 publications

TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo

TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo

Ubiquitin-mediated activation of TAK1 and IKK

Mechanism of p38 MAP kinase activation in vivo

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