Structural Basis for the Interaction of TAK1 Kinase with its Activating Protein TAB1

Brown, K. N.; Vial, Sarah; Dedi, Neesha; Long, Joanna; Dunster, Nicholas J.; Cheetham, G.M.T.

doi:10.1016/j.jmb.2005.09.098

Cited by 80 publications

(86 citation statements)

References 24 publications

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“…We generated a constitutively active form of TAK1 by expressing and purifying from insect cells a fused TAK1 construct containing the kinase domain of TAK1 fused to the TAK1-activating domain of binding partner TAB1 (Fig. 1A) (17). We will refer to this fusion construct as TAK1 f , with WT indicating no mutations to the gatekeeper residue.…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

“…TAK1 was expressed in SF9 cells and purified as previously described (17). Covalent capture of TAK1 substrates was performed on 2 mg of lysate per sample labeled with 1% (wt/wt) of purified TAK1 and 250 μM N 6 -furfuryl-ATPγS.…”

Section: Methodsmentioning

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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“…2) (2). This interaction is shown by the crystal structure of a TAK1-TAB1 fusion protein (14). Although TAB1 does not display homology to any other protein in the human proteome, the crystal structure of the individual TAB1 protein revealed that it contains folds with most similarity to the protein phosphatase PP2Ca; however, importantly, TAB1 is devoid of phosphatase activity because critical residues are missing (15).…”

Section: Tab1 and Tak1 Activitymentioning

confidence: 98%

TAK1, more than just innate immunity

et al. 2012

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SummaryTransforming growth factor b-activated kinase 1 (TAK1) is a key regulator of the innate immunity and the proinflammatory signaling pathway. In response to interleukin-1, tumor necrosis factor-a, and toll-like receptor agonists, it mediates the activation of the nuclear factor jB (NF-jB), c-Jun N-terminal kinase (JNK), and p38 pathways. In addition, TAK1 plays a central role in adaptive immunity, in which it mediates signaling from T-and B-cell receptors. This review will focus on recent developments and also examine the regulation of TAK1 in response to a diverse range of other stimuli including DNA damage, transforming growth factor-b, Wnt, osmotic stress, and hypoxia.2012 IUBMB IUBMB Life, 64(10): [825][826][827][828][829][830][831][832][833][834] 2012

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“…In response to these pro-inflammatory stimuli, active TAK1 forms a complex with an accessory protein TAB1 (Brown et al, 2005), and activated TAK1 phosphorylates MKK4 and MKK6, thereby promoting JNK and p38 activation, respectively (Shim et al, 2005). TAK1 signaling complexes include the adaptor proteins TAB2 and TAB3, as well as the E3 ubiquitin ligase/ scaffold protein TRAF6 (Wang et al, 2001).…”

Section: Tak1mentioning

confidence: 99%

Role of mitogen-activated protein kinase kinase kinases in signal integration

2007

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Mitogen-activated protein kinases (MAPKs) are members of a dynamic protein kinase network through which diverse stimuli regulate the spatio-temporal activities of complex biological systems. MAPKs regulate critical cellular functions required for homeostasis such as the expression of cytokines and proteases, cell cycle progression, cell adherence, motility and metabolism. MAPKs therefore influence cell proliferation, differentiation, survival, apoptosis and development. In vertebrates, five MAPK families are regulated by MAPK kinase kinase-MAPK kinase-MAPK (MKKK-MKK-MAPK) phosphorelay systems. There are at least 20 MKKKs that selectively phosphorylate and activate different combinations of the seven MKKs, resulting in a specific activation profile of members within the five MAPK families. MKKKs are differentially activated by upstream stimuli including cytokines, antigens, toxins and stress insults providing a mechanism to integrate the activation of different MAPKs with the cellular response to each stimulus. Thus, MKKKs can be considered as 'signaling hubs' that regulate the specificity of MAPK activation. In this review, we describe how the MKKK 'hub' function regulates the specificity of MAPK activation, highlighting MKKKs as targets for therapeutic intervention in cancer and other diseases.

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Structural Basis for the Interaction of TAK1 Kinase with its Activating Protein TAB1

Cited by 80 publications

References 24 publications

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

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

TAK1, more than just innate immunity

Role of mitogen-activated protein kinase kinase kinases in signal integration

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