Identification and Characterization of a Novel MAP Kinase Kinase Kinase, MLTK

Gotoh, Isamu; Adachi, Makoto; Nishida, Eisuke

doi:10.1074/jbc.m008595200

Cited by 107 publications

(102 citation statements)

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“…For example, MLK family members mediate the activation of p38 as well as JNK MAPK pathways by multiple stimuli, including cellular stresses (Kyriakis and Avruch, 2001). One of these, MLTK␤, induces actin cytoskeleton reorganization through the p38 MAPK pathway and is activated by osmotic stress (Gotoh et al, 2001). Furthermore, the p38 MAPK pathway directly phosphorylates the actin polymerization modifier HSP27 and regulates actin reorganization Huot, 1995, 1999).…”

Section: Discussionmentioning

confidence: 99%

Section: Identification Of the Novel Protein Kinase Sapk␣mentioning

confidence: 99%

“…However, the kinase domain showed the highest homology to MEKK family members in mammals and plants ( Figure 1B). Among these are EDR1 (36% identity, 51% similar), which negatively regulates defense responses in plants (Frye et al, 2001); mammalian MLTK␣ (also known as ZAK, 34% identity, 54% similar), an MEKK that can activate the ERK, JNK/SAPK, p38, and ERK5 pathways (Gotoh et al, 2001); CTR1 (36% identity, 51% similar), a RAF-like kinase and a negative regulator of ethylene response in plants (Kieber et al, 1993); and MAP3K10 (also known as MST/MLK2, 34% identity, 50% similar), a member of the MLK family which directly phosphorylates and activates SEK1, an activator of JNK/SAPK (Hirai et al, 1997). MLTK␣ also has a SAM domain; however, unlike SAPK␣, the MLTK␣ SAM domain is C-terminal to the kinase domain ( Figure 1C).…”

Section: Identification Of the Novel Protein Kinase Sapk␣mentioning

confidence: 99%

“…Several members of this kinase family activate JNK/SAPK stress signaling pathways. Recently, MLK family kinases (MLTK/ZAK) were reported to activate the JNK/SAPK and p38 pathways (Gotoh et al, 2001;Gallo and Johnson, 2002). MLTKs are activated by osmotic shock, and overexpression of MLTK␣, but not MLTK␤, induces the disruption of actin stress fibers and dramatic changes in cell morphology mediated through the p38 MAP kinase pathway (Gotoh et al, 2001).…”

mentioning

confidence: 99%

“…Recently, MLK family kinases (MLTK/ZAK) were reported to activate the JNK/SAPK and p38 pathways (Gotoh et al, 2001;Gallo and Johnson, 2002). MLTKs are activated by osmotic shock, and overexpression of MLTK␣, but not MLTK␤, induces the disruption of actin stress fibers and dramatic changes in cell morphology mediated through the p38 MAP kinase pathway (Gotoh et al, 2001). Dictyostelium grows as single-celled amoebae, which, upon starvation, aggregate to form a multicellular organism (Aubry and Firtel, 1999;Chen et al, 1996).…”

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confidence: 99%

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DictyosteliumStress-activated Protein Kinase α, a Novel Stress-activated Mitogen-activated Protein Kinase Kinase Kinase-like Kinase, Is Important for the Proper Regulation of the Cytoskeleton

Sun

Firtel

2003

MBoC

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Mitogen-activated protein kinase cascades regulate various cellular functions, including growth, cell differentiation, development, and stress responses. We have identified a new Dictyostelium kinase (stress-activated protein kinase [SAPK]␣), which is related to members of the mixed lineage kinase class of mitogen-activated protein kinase kinases. SAPK␣ is activated by osmotic stress, heat shock, and detachment from the substratum and by a membrane-permeable cGMP analog, a known regulator of stress responses in Dictyostelium. SAPK␣ is important for cellular resistance to stresses, because SAPK␣ null cells exhibit reduced viability in response to osmotic stress. We found that SAPK␣ mutants affect cellular processes requiring proper regulation of the actin cytoskeleton, including cell motility, morphogenesis, cytokinesis, and cell adhesion. Overexpression of SAPK␣ results in highly elevated basal and chemoattractant-stimulated F-actin levels and strong aggregation and developmental defects, including a failure to polarize and chemotax, and abnormal morphogenesis. These phenotypes require a kinase-active SAPK␣. SAPK␣ null cells exhibit reduced chemoattractant-stimulated F-actin levels, cytokinesis, developmental and adhesion defects, and a motility defect that is less severe than that exhibited by SAPK␣-overexpressing cells. SAPK␣ colocalizes with F-actin in F-actin-enriched structures, including membrane ruffles and pseudopodia during chemotaxis. Although SAPK␣ is required for these F-actin-mediated processes, it is not detectably activated in response to chemoattractant stimulation. INTRODUCTIONThe actin cytoskeleton plays a vital role in numerous cellular processes, such as cell locomotion, phagocytosis, cytokinesis, cell adhesion, cell shape changes, and stress responses. During these processes, the actin cytoskeleton is dynamically changed, a process that involves F-actin polymerization and depolymerization and the reorganization of existing filament networks. Mutations of signaling molecules or structural elements involved in these changes affect cellular processes to various extents.Eukaryotic cells are constantly exposed to stress conditions. To survive, cells adopt various mechanisms to adapt to environmental changes. Mitogen-activated protein kinase (MAPK) pathways regulate cellular responses to external stress in various organisms, including yeast, plants, and mammals (Canman and Kastan, 1996;Jonak et al., 1996;Gustin et al., 1998;Hirt, 2000;Kyriakis and Avruch, 2001;O'Rourke et al., 2002). In Saccharomyces cerevisiae, the wellcharacterized HOG1 MAPK pathway is activated by osmotic stress and leads to gene expression and glycerol production, which is critical for yeast cells to withstand osmotic stress (Gustin et al., 1998;O'Rourke et al., 2002). In mammalian cells, the c-Jun NH 2 -terminal kinase/stress-activated protein kinase (JNK/SAPK1) pathway and the p38/SAPK2 MAP kinase pathway are both activated by diverse stimuli including UV, osmotic, and thermal stresses (Canman and Kastan, 1996;Chang and Kari...

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Section: Discussionmentioning

confidence: 99%

Section: Identification Of the Novel Protein Kinase Sapk␣mentioning

confidence: 99%

Section: Identification Of the Novel Protein Kinase Sapk␣mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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DictyosteliumStress-activated Protein Kinase α, a Novel Stress-activated Mitogen-activated Protein Kinase Kinase Kinase-like Kinase, Is Important for the Proper Regulation of the Cytoskeleton

Sun

Firtel

2003

MBoC

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The Detection of MAPK Signaling

Shaul

Seger

2006

CP Molecular Biology

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Mitogen-activated protein kinase (MAPK) cascades are central pathways that participate in the intracellular transmission of extracellular signals. Each of the MAPK signaling cascades seems to consist of three to five tiers of protein kinases that sequentially activate each other by phosphorylation. Since the majority of MAPK cascade components are kinases, the methods used to detect their activation involve determining phosphorylation state and protein kinase activities. The primary method describes the use of immunoblotting with specific anti-phospho antibody to detect activation of MAPK components. Alternative methods described are immunoprecipitation of desired protein kinases followed by phosphorylation of specific substrates and the use of an in-gel kinase assay. These methods have proven useful in the study of the MAPK signaling cascades.

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The Detection of MAPK Signaling

Shaul

Seger

2005

CP Cell Biology

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Mitogen‐activated protein kinase (MAPK) cascades are central pathways that participate in the intracellular transmission of extracellular signals. Each of the MAPK signaling cascades seems to consist of three to five tiers of protein kinases that sequentially activate each other by phosphorylation. Since the majority of MAPK cascade components are kinases, the methods used to detect their activation involve determining phosphorylation state and protein kinase activities. The Basic Protocol describes the use of immunoblotting with specific anti‐phospho antibody to detect activation of MAPK components. Alternative methods described are immunoprecipitation of desired protein kinases followed by phosphorylation of specific substrates and the use of an in‐gel kinase assay. These methods have proven useful in the study of the MAPK signaling cascades.

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Identification and Characterization of a Novel MAP Kinase Kinase Kinase, MLTK

Cited by 107 publications

References 43 publications

DictyosteliumStress-activated Protein Kinase α, a Novel Stress-activated Mitogen-activated Protein Kinase Kinase Kinase-like Kinase, Is Important for the Proper Regulation of the Cytoskeleton

DictyosteliumStress-activated Protein Kinase α, a Novel Stress-activated Mitogen-activated Protein Kinase Kinase Kinase-like Kinase, Is Important for the Proper Regulation of the Cytoskeleton

The Detection of MAPK Signaling

The Detection of MAPK Signaling

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