MEKKs, GCKs, MLKs, PAKs, TAKs, and Tpls: upstream regulators of the c-Jun amino-terminal kinases?

Fanger, Gary R.; Gerwins, Pär; Widmann, Christian; Jarpe, Matthew; Johnson, Gary L.

doi:10.1016/s0959-437x(97)80111-6

Cited by 311 publications

(261 citation statements)

References 55 publications

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“…Various growth factors, stress-inducing agents and apoptotic triggers have been demonstrated to a ect the activity of several MAP kinases such as ERK1/2 as well as stress-activated kinases (Davis, 1993;Fanger et al, 1997;Hughes, 1995;Xia et al, 1995). To test whether SLK activity could be modulated by such factors, Myc epitope-tagged SLK was transfected into 293 cells followed by stimulation with various factors and stress inducing agents in the absence of serum (see Figure 6a).…”

Section: Modulation Of Slk Activity By Extracellular Stimulimentioning

confidence: 99%

“…Immunoprecipitations and in vitro kinase assays following overexpression of SLK in 293 cells showed that it activated isoforms of JNK1. As for SLK, the Ste20-related kinase p65PAK also activates the stress response pathway (Fanger et al, 1997). Similarly, activation of the related kinases MST1/2 activates the p38 MAPK pathway (Creasy and Cherno , 1995;Graves et al, 1998).…”

Section: No Reactivity Was Observed In Vector Transfected Cells (C)mentioning

confidence: 99%

“…The activation, or inhibition of various pathways results in the expression of speci®c subsets of genes directly involved in proliferation or terminal di erentiation (Davis, 1993;Fanger et al, 1997). Extracellular signals acting on growth factor receptors or G-protein coupled receptors transduce their e ect through a kinase cascade resulting in the activation of mitogen-activated protein kinases (MAPK) (Davis, 1993).…”

Section: Introductionmentioning

confidence: 99%

“…Extracellular signals acting on growth factor receptors or G-protein coupled receptors transduce their e ect through a kinase cascade resulting in the activation of mitogen-activated protein kinases (MAPK) (Davis, 1993). Stress-inducing agents as well as apoptotic triggers have been demonstrated to signal through stress-responsive pathways leading to the activation of stress-activated protein kinases such as c-Jun amino-terminal kinases (JNKs) and p38 (Fanger et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Induction of apoptosis by SLK, a Ste20-related kinase

1999

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We have cloned and characterized a novel murine Ste20-related kinase designated SLK. SLK displays high homology to the Ste20-related kinase LOK, and is more distantly related to MST1 and 2, both Ste20-like kinases. In addition, SLK displays high homology to microtubule and nuclear associated protein (M-NAP) and AT1-46, both of unknown function. SLK is ubiquitously expressed as multiple mRNAs in tissues and cell lines and is downregulated by mitogen depletion in di erentiating myoblasts. Biochemical characterization showed that SLK overexpression activates c-Jun amino-terminal kinase 1 (JNK1). However, in vitro kinase assays indicated that SLK was not activated in response to various growth factors or stress-inducing agents. Immuno¯uorescence studies revealed that SLK colocalized to distinct cytosolic domains, preferentially at the periphery of the cells. In addition, prolonged overexpression of SLK in cultured ®broblasts resulted in apoptosis as demonstrated by annexin-V and TUNEL staining. Our results suggest that SLK belongs to a new family of protein kinases, mediating activation of the stress response pathway through a novel signaling cascade.

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Section: Modulation Of Slk Activity By Extracellular Stimulimentioning

confidence: 99%

Section: No Reactivity Was Observed In Vector Transfected Cells (C)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Induction of apoptosis by SLK, a Ste20-related kinase

1999

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“…The JNK/SAPK pathway is activated in response to a wide variety of stimuli such as transforming growth factor-b (TGF-b) and several forms of environmental stress, including the in¯ammatory cytokines tumour necrosis factor a (TNFa) and Interleukin-1 (IL-1), osmotic shock, ultraviolet light, g radiation, and protein synthesis inhibitors (Fanger et al, 1997). Like ERKs, the activated JNK/SAPKs translocate to the nucleus where they phosphorylate transcription factors such as c-Jun (DeÂ rijard et al, 1994) and ATF2 (Gupta et al, 1995;van Dam et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

The oncogenic TEL/PDGFRβ fusion protein induces cell death through JNK/SAPK pathway

et al. 1999

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Immunolocalization of the mitogen-activated protein kinases p42MAPK and JNK1, and their regulatory kinases MEK1 and MEK4, in adult rat central nervous system

Flood¹,

Finn²,

Walton³

et al. 1998

J. Comp. Neurol.

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Cell survival, death, and stress signals are transduced from the cell surface to the cytoplasm and nucleus via a cascade of phosphorylation events involving the mitogen-activated protein kinase (MAPK) family. We compared the distribution of p42 mitogen-activated protein kinase (p42MAPK) and its activator MAPK or ERK kinase (MEK1; involved in transduction of growth and differentiation signals), with c-Jun N-terminal kinase (JNK1) and its activator MEK4 (involved in transduction of stress and death signals) in the adult rat central nervous system. All four kinases were present in the cytoplasm, dendrites, and axons of neurons. The presence of p42MAPK and JNK1 in dendrites and axons, as well as in cell bodies, suggests a role for these kinases in phosphorylation and regulation of cytoplasmic targets. A high degree of correspondence was found between the regional distribution of MEK1 and p42MAPK. Immunostaining for MEK1 and p42MAPK was intense in olfactory structures, neocortex, hippocampus, striatum, midline, and interlaminar thalamic nuclei, hypothalamus, brainstem, Purkinje cells, and spinal cord. In addition to neurons, p42MAPK was also present in oligodendrocytes. Whereas MEK4 was ubiquitously distributed, JNK1 was more selective. Immunostaining for MEK4 and JNK1 was intense in the olfactory bulb, lower cortical layers, the cholinergic basal forebrain, most nuclei of the thalamus, medial habenula, and cranial motor nuclei. The distribution of MEK1 and p42MAPK proteins only partially overlapped with that of MEK4 and JNK1. This suggests that the growth/differentiation and death/stress pathways affected by these kinases may not necessarily act to counterbalance each other in response to extracellular stimuli. The differential distribution of these kinases may control the specificity of neuronal function to extracellular signals.

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MEKKs, GCKs, MLKs, PAKs, TAKs, and Tpls: upstream regulators of the c-Jun amino-terminal kinases?

Cited by 311 publications

References 55 publications

Induction of apoptosis by SLK, a Ste20-related kinase

Induction of apoptosis by SLK, a Ste20-related kinase

The oncogenic TEL/PDGFRβ fusion protein induces cell death through JNK/SAPK pathway

Immunolocalization of the mitogen-activated protein kinases p42MAPK and JNK1, and their regulatory kinases MEK1 and MEK4, in adult rat central nervous system

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