MST/MLK2, a Member of the Mixed Lineage Kinase Family, Directly Phosphorylates and Activates SEK1, an Activator of c-Jun N-terminal Kinase/Stress-activated Protein Kinase

Hirai, Syu Ichi; Katoh, Masaru; Terada, Masaaki; Kyriakis, John; Zon, Leonard I.; Rana, Ajay; Avruch, Joseph; Ohno, Shigeo

doi:10.1074/jbc.272.24.15167

Cited by 160 publications

(130 citation statements)

References 35 publications

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“…The mouse homolog of this gene, DLK (Holzman et al, 1994), and the rat homolog, MUK (Hirai et al, 1996), have also been isolated, and have been shown to be associated with the JNK/SAPK pathway Hirai et al, 1997). We now report that ZPK phosphorylates CREB both in vitro and in vivo and forms an immunoprecipitable complex with CREB and inhibits PKA-induced transcriptional activation by CREB.…”

Section: Introductionmentioning

confidence: 64%

ZPK inhibits PKA induced transcriptional activation by CREB and blocks retinoic acid induced neuronal differentiation

et al. 1999

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Zipper Protein Kinase (ZPK) is a leucine zipper protein localized to the nucleus which exhibits serine-threonine kinase activity and is associated with the stress dependent signal transduction pathway. ZPK forms heterodimers with leucine zipper containing transcription factors such as the cyclic AMP responsive element binding protein (CREB) and Myc. Furthermore ZPK phosphorylates both Myc and CREB. Overexpression of ZPK in NTera-2 human teratocarcinoma cells results in inhibition of PKA induced transcriptional activation by CREB and prevents retinoic acid induced di erentiation of the cells to neurons. Our results suggest that ZPK sti¯es neural di erentiation of NT-2 cells partly due to its inhibitory e ect on CREB function.

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Section: Introductionmentioning

confidence: 64%

ZPK inhibits PKA induced transcriptional activation by CREB and blocks retinoic acid induced neuronal differentiation

et al. 1999

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“…These include TAK1 [33], ASK1/MAPKKK5 [34], DLK/MUK/ZPK [35,36], and MEKK4 [35,37,38]. Overexpression of these MAP3Ks leads to activation of both p38 and JNK pathways which is possibly one reason why these two pathways are often co-activated.…”

Section: Further Upstream Activatorsmentioning

confidence: 99%

“…Rac1 can bind to MEKK1 or MLK1 while Cdc42 can only bind to MLK1 and both result in activation of p38 via MAP3Ks [35,42]. p21-activated kinases (PAKs) are yet another group of p38 activators.…”

Section: Further Upstream Activatorsmentioning

confidence: 99%

Activation and signaling of the p38 MAP kinase pathway

2005

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The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation. We focus on the role of p38 as a signal transduction mediator and examine the evidence linking p38 to inflammation, cell cycle, cell death, development, cell differentiation, senescence and tumorigenesis in specific cell types. Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38.

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“…In contrast to MAPKs and MAPKKs, the MAPKKKs in the JNK and p38 modules are highly divergent in structure and gene number. To date, eleven di erent MAPKKKs have been identi®ed as upstream activators of JNK pathway (Widmann et al, 1999); MEKK1 (Lange et al, 1993), MEKK2 (Blank et al, 1996), MEKK3 (Blank et al, 1996), MTK1/ MEKK4 (Takekawa et al, 1997;Gerwins et al, 1997), Tpl-2/Cot (Aoki et al, 1991;Salmeron et al, 1996), MUK/DLK/ZPK Holzman et al, 1994;Reddy and Pleasure, 1994), MLK-2/MST (Dorow et al, 1995;Hirai et al, 1997), MLK-3/SPRK/ PTK-1 (Rana et al, 1996;Gallo et al, 1994;Ing et al, 1994), TAK1 (Yamaguchi et al, 1995), ASK1/ MAPKKK5 Ichijo et al, 1997) and ASK2 (Saitoh and Ichijo, unpublished observation)/MAPKKK6 (Wang et al, 1998) have been shown to activate JNKs by overexpression (Figure 1). Of these, MEKK1, MEKK2, MEKK3 and Tpl-2 can also activate the ERK pathway, while only TAK1, ASK1 and MTK1 have been shown to strongly activate p38s as well.…”

Section: Upstream Kinases In the Jnk And P38 Modulesmentioning

confidence: 99%

From receptors to stress-activated MAP kinases

1999

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The cell signaling pathways that culminate in activation of a family of stress-activated MAP kinases are beginning to be de®ned. Determination of cell life and cell death is known to largely depend on the balance of intrinsic life and death signals within cells. Recently, two representative mammalian stress-activated kinases, the JNK and p38 MAP kinases, have been implicated in determination of cell fate by modifying the life, death and di erentiation signals. However, the molecular mechanisms by which extracellular signals are transmitted from membrane receptors to the most upstream kinases in the JNK and p38 signaling modules are not fully understood. This review will provide an overview of current knowledge of molecular links between in¯amma-tory cyokine receptors and stress-activated MAP kinase cascades.

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MST/MLK2, a Member of the Mixed Lineage Kinase Family, Directly Phosphorylates and Activates SEK1, an Activator of c-Jun N-terminal Kinase/Stress-activated Protein Kinase

Cited by 160 publications

References 35 publications

ZPK inhibits PKA induced transcriptional activation by CREB and blocks retinoic acid induced neuronal differentiation

ZPK inhibits PKA induced transcriptional activation by CREB and blocks retinoic acid induced neuronal differentiation

Activation and signaling of the p38 MAP kinase pathway

From receptors to stress-activated MAP kinases

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