Independent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms

Dérijard, Benoı̂t; Raingeaud, Joël; Barrett, Tamera; Wu, I-Huan; Han, Jiahuai; Ulevitch, Richard J.; Davis, Roger J.

doi:10.1126/science.7839144

Cited by 1,490 publications

(1,247 citation statements)

References 28 publications

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“…JNKs are activated by two distinct MAPKKs, MKK4/SEK1 (Sanchez et al, 1994;Derijard et al, 1995), and MKK7 Yao et al, 1997;Wu et al, 1997;Tournier et al, 1997;Holland et al, 1997), in the JNK signaling unit. The p38 subgroup is composed of four genes including p38a, p38b, p38g and p38d (Han et al, 1994;Lee et al, 1994;Jiang et al, 1997;Stein et al, 1997;Goedert et al, 1997;Wang et al 1997).…”

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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Section: Upstream Kinases In the Jnk And P38 Modulesmentioning

confidence: 99%

From receptors to stress-activated MAP kinases

1999

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“…The patterns of activation described above are in accord with the view that ERKs are activated by a separate chain of kinases, whereas JNK/SAPKs and p38/RK may have an upstream activator(s) in common, and hence be activated together. Three potential activators of p38/RK have been described, namely the MAP kinase kinase homologues MKK4/ SEK1, MKK3 and MKK6 (SaÂ nchez et al, 1994;DeÂ rijard et al, 1995;Cuenda et al, 1996;Raingeaud et al, 1996). Current evidence indicates that MKK4/ SEK1, one of whose upstream activators may be MEKK1 (Yan et al, 1994;Lin et al, 1995) may be the physiological activator of JNK/SAPKs but not p38/ RK because expression of the MEKK1 in COS or HeLa cells triggers the activation of JNK/SAPKs but not p38/RK Lin et al, 1995).…”

Section: Selective Activation Of Erk Jnk/sapk and P38/rk Map Kinasementioning

confidence: 99%

Effects of the inhibition of p38/RK MAP kinase on induction of five fos and jun genes by diverse stimuli

et al. 1997

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The ERK, JNK/SAPK and p38/RK MAP kinase subtypes are di erentially activated by physiological, pharmacological and stress stimuli; all three subtypes are implicated in immediate-early (IE) gene induction by these agents. Here, we have asked whether inhibition of a single MAP kinase subtype under these conditions would generally alter induction of several IE genes in a similar way or whether this would di erentially up-and down-regulate particular IE genes, an issue which bears on the question of whether individual MAP kinases are strictly targeted to speci®c IE genes, or whether they might catalyse phosphorylation events that a ect several IE genes in the same way. SB 203580, an inhibitor of p38/RK, has been used to analyse the role of this kinase in the induction of ®ve IE genes (c-fos, fosB, c-jun, junB and junD) under diverse conditions of stimulation. In C3H 10T cells, p38/RK and its downstream kinase MAPKAP K-2 are activated by all stimuli used with the exception of TPA. The speci®city of SB 203580 as a p38/RK inhibitor in these cells is demonstrated; it does not a ect ERKs or JNK/SAPKs but does result in a small increase in the activity of the upstream kinase MKK6, the principal p38/RK activator in these cells. We ®nd that inhibition of p38/RK under these conditions produces general e ects on all ®ve IE genes as a group in three ways. First, induction of all ®ve genes in response to okadaic acid or tumour necrosis factor-a (TNF-a) is not signi®cantly altered by SB 203580. Second, in cells stimulated with anisomycin or U.V. radiation, SB 203580 potently inhibits all of the induced IE genes. Finally, SB 203580 enhances induction of all ®ve IE genes in EGF-treated cells; these enhanced mRNA levels are not due to stabilisation of labile mRNA transcripts. The signi®cance of these results to current thinking on the relationship between distinct MAP kinase subtypes and speci®c IE genes is discussed.

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“…The JNK/SAPK have been shown to phosphorylate and regulate the activity of several transcription factors including c-jun, ELK-1 and ATF-2 Hibi et al, 1993;Sluss et al, 1994;Johnson and Vaillancourt, 1994;Witmarsh et al, 1995). Similar to the ERK members of the MAPK family, JNK/SAPK is a component of a sequential protein kinase pathway (Kyriakis et al, 1992Sluss et al, 1994;Yan et al, 1994;DeÂ rijard et al, 1995;Gupta et al, 1995;Lange-Carter et al, 1993). JNK/ SAPK is phosphorylated resulting in its activation, by JNK kinase (JNKK/stress-activated ERK kinase, SEK-1) DeÂ rijard et al, 1995;Lin et al, 1995;Sanchez et al, 1994).…”

mentioning

confidence: 99%

“…Similar to the ERK members of the MAPK family, JNK/SAPK is a component of a sequential protein kinase pathway (Kyriakis et al, 1992Sluss et al, 1994;Yan et al, 1994;DeÂ rijard et al, 1995;Gupta et al, 1995;Lange-Carter et al, 1993). JNK/ SAPK is phosphorylated resulting in its activation, by JNK kinase (JNKK/stress-activated ERK kinase, SEK-1) DeÂ rijard et al, 1995;Lin et al, 1995;Sanchez et al, 1994). JNKK/SEK-1 is itself regulated by phosphorylation by an upstream kinase referred to as MEK kinase (MEKK) (LangeCarter et al, 1993).…”

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confidence: 99%

Cisplatin induces a persistent activation of JNK that is related to cell death

1998

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Genotoxic stress triggers signalling pathways that either mediate cell killing or protection of a ected cells. While induction of p53 is observed for most of the genotoxins, activation of MAPK/SAPK cascades is not a general response. The role of MAPK/SAPK activation on cell fate, seems to be dependent, in some systems, on the balanced response among both cascades. We have here examined the e ect of cis and trans-DDP on the activation of ERK and JNK activities. While no signi®cant induction of ERK was observed with the compounds, both of them are able to strongly activate JNK. Trans-DDP response is rapid and transient while the cis-DDP one is slow and persistent. In contrast with the observed nuclear translocation of JNK in response to U.V. light, none of the platinum compounds induces translocation, on the contrary, activation of JNK occurs in both the nuclear and cytoplasmic compartments. Inhibition of tyrosine phosphatases by orthovanadate pretreatment prolongs the time of JNK induction in response to both platinum compounds. The positive modulation of JNK activation correlates with an increase in toxicity that, for cis-DDP corresponds to a tenfold decrease in the IC 50 . A strong increase in MKP-1 levels was observed only in response to trans-DDP suggesting the involvement of this activity in the downregulation of JNK activity in response to this compound. Altogether the results suggest that the prolonged activation of JNK in response to cis-DDP contributes to cell death induction.

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Independent Human MAP-Kinase Signal Transduction Pathways Defined by MEK and MKK Isoforms

Cited by 1,490 publications

References 28 publications

From receptors to stress-activated MAP kinases

From receptors to stress-activated MAP kinases

Effects of the inhibition of p38/RK MAP kinase on induction of five fos and jun genes by diverse stimuli

Cisplatin induces a persistent activation of JNK that is related to cell death

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