TNIK, a Novel Member of the Germinal Center Kinase Family That Activates the c-Jun N-terminal Kinase Pathway and Regulates the Cytoskeleton

Fu, Chong; Shen, Mary; Huang, Betty; Lasaga, Joe; Payan, Donald G.; Luo, Ying

doi:10.1074/jbc.274.43.30729

Cited by 177 publications

(204 citation statements)

References 26 publications

(45 reference statements)

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“…This gene encodes a protein belonging to the mammalian germinal center kinases (GCK) family, interacting Letters to the Editor with both Traf2 and NCK, and able to specifically activate the Jun N-terminal kinase domain pathway. 8 In conclusion, we hypothesize that, following the t(3;12) rearrangement, the translocation of the promoter and the 5 0 portion of TNIK downstream to HMGA2 leads to the activation of the latter gene as a consequence of a position effect. …”

mentioning

confidence: 82%

t(3;12)(q26;q14) in polycythemia vera is associated with upregulation of the HMGA2 gene

Storlazzi

Albano

Locunsolo³

et al. 2006

Leukemia

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mentioning

confidence: 82%

t(3;12)(q26;q14) in polycythemia vera is associated with upregulation of the HMGA2 gene

Storlazzi

Albano

Locunsolo³

et al. 2006

Leukemia

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“…In particular, GCKs of the group II do not stimulate any of the currently known MAPK pathways. 145 Several group I GCKs (germinal center kinase (GCK), 146 GCK-like kinase (GLK), 147 GCK-related (GCKR), 148 HPK/GCK-like kinase (HGK), 149 NIK-like embryo-specific kinase (NESK), 150 TRAF2 and Nck-interacting kinase (TNIK) 151 ) have been implicated in TNF-mediated JNK activation because of the following findings: they become activated by TNF (NESK, HGK, GCKR, GLK), interact with TRAF2 (TNIK, GCK, GCKR 152 ) and dominant-negative mutants of these kinases interfere with TNF-induced JNK activation (NESK, HGK, GCKR). The group I GCKs seem to channel stimulation of TNF-R1 to the JNK cascade by concomitant interaction with TRAF2 and MEKK1 and phosphorylation-dependent activation of the latter.…”

Section: Ap-1mentioning

confidence: 99%

“…For example, the various GCKs, which have been implicated in TNF-induced activation of JNK, are unable to stimulate the p38-MAPK cascade. 147,[149][150][151]161 In addition, it has been shown that a deletion mutant of RIP, lacking its intermediate domain, interferes with TRAF2-mediated activation of p38-MAPK, but failed to inhibit TRAF2-induced JNK activation. 146 Thus, TNF may signal p38-MAPK activation via an axis comprising TRAF2 and RIP, whereas JNK activation occurs via TRAF2-GCKs-MEKK1/ASK1.…”

Section: Ap-1mentioning

confidence: 99%

Tumor necrosis factor signaling

2003

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A single mouse click on the topic tumor necrosis factor (TNF) in PubMed reveals about 50 000 articles providing one or the other information about this pleiotropic cytokine or its relatives. This demonstrates the enormous scientific and clinical interest in elucidating the biology of a molecule (or rather a large family of molecules), which began now almost 30 years ago with the description of a cytokine able to exert antitumoral effects in mouse models. Although our understanding of the multiple functions of TNF in vivo and of the respective underlying mechanisms at a cellular and molecular level has made enormous progress since then, new aspects are steadily uncovered and it appears that still much needs to be learned before we can conclude that we have a full comprehension of TNF biology. This review shortly covers some general aspects of this fascinating molecule and then concentrates on the molecular mechanisms of TNF signal transduction. In particular, the multiple facets of crosstalk between the various signalling pathways engaged by TNF will be addressed.

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“…Proline-and alanine-rich STE20-related kinase associates with actin, and prostate-derived STE20-like kinase (PSK), Traf2-and Nckinteracting kinase, and STE20-like kinase (SLK) decrease actin stress fibers and focal adhesions and inhibit cell spreading (3,(13)(14)(15). SLK has recently been shown to associate with MTs at the cell periphery (16).…”

mentioning

confidence: 99%

The Prostate-derived Sterile 20-like Kinase (PSK) Regulates Microtubule Organization and Stability

Mitsopoulos¹,

Zihni²,

Garg

et al. 2003

Journal of Biological Chemistry

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Sterile 20 (STE20) protein kinases, which include germinal center kinases and p21-activated protein kinases, are known to activate mitogen-activated protein kinase pathways (c-Jun NH 2 -terminal kinase, p38, or extracellular signal-regulated kinase), leading to changes in gene transcription. Some STE20s can also regulate the cytoskeleton, and we have shown that the germinal center kinase-like kinase prostate-derived STE20-like kinase (PSK) affects actin cytoskeletal organization. Here, we demonstrate that PSK colocalizes with microtubules; and that this localization is disrupted by the microtubule depolymerizing agent nocodazole. The association of PSK with microtubules results in the production of stabilized perinuclear microtubule cables that are nocodazole-resistant and contain increased levels of acetylated ␣-tubulin. Recent work has demonstrated that some STE20s can also regulate the cell cytoskeleton. PAKs interact with Rac or Cdc42 GTPases via the CRIB domain and act as downstream effectors for these small GTP binding proteins to regulate the actin cytoskeleton (reviewed in Refs. 4, 5). Rac and Cdc42 stimulated morphological rearrangements are blocked by mutated PAK, and activated PAK down-regulates actin stress fibers and focal complexes (6 -8). Some of the effects of PAK1 can be attributed to the phosphorylation of downstream kinases, such as myosin light chain kinase, which reduces its activity toward myosin light chain, and LIM kinase 1, which phosphorylates and inactivates the actin depolymerizing protein cofilin to generate actin clusters (9, 10). X-PAK5 co-localizes to actin and microtubules (MTs) and produces stabilized MTs that are associated in bundles, and PAK1 accumulates at the MT-organizing center and along mitotic spindles during mitosis (11,12).Although GCK-like STE20s lack a CRIB domain, recent work has demonstrated that members of this subfamily of STE20s can also regulate the actin cytoskeleton. Proline-and alanine-rich STE20-related kinase associates with actin, and prostate-derived STE20-like kinase (PSK), Traf2-and Nckinteracting kinase, and STE20-like kinase (SLK) decrease actin stress fibers and focal adhesions and inhibit cell spreading (3,(13)(14)(15). SLK has recently been shown to associate with MTs at the cell periphery (16).There is increasing evidence that actin filaments and MTs are coordinately regulated during the establishment and maintenance of cell polarity, division, and motility. The ability of MTs to undergo transitions between growth, shrinkage and pause are crucial for their function and the regulation of these processes. MT dynamics and stability are controlled by multiple factors, which include MT-associated proteins (MAPs), MTaffinity regulated kinases, severing factors (e.g. katanin), and catastrophe proteins (e.g. stathmin/OP18 and XKCM1) (reviewed in (17)). MAPs provide a focal point for MT regulation and act as structural proteins that lack enzymatic activity but promote the assembly of tubulin and MT stability. The affinity of MAPs for MTs is controlled by...

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TNIK, a Novel Member of the Germinal Center Kinase Family That Activates the c-Jun N-terminal Kinase Pathway and Regulates the Cytoskeleton

Abstract: Germinal center kinases (GCKs

Cited by 177 publications

References 26 publications

t(3;12)(q26;q14) in polycythemia vera is associated with upregulation of the HMGA2 gene

t(3;12)(q26;q14) in polycythemia vera is associated with upregulation of the HMGA2 gene

Tumor necrosis factor signaling

The Prostate-derived Sterile 20-like Kinase (PSK) Regulates Microtubule Organization and Stability

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