Selective interaction of JNK protein kinase isoforms with transcription factors.

Gupta, Shashi; Barrett, Tamera; Whitmarsh, Alan J.; Cavanagh, Julie; Sluss, Hayla Karen; Dérijard, Benoı̂t; Davis, Roger J.

doi:10.1002/j.1460-2075.1996.tb00636.x

Cited by 1,249 publications

(1,118 citation statements)

References 53 publications

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“…Several kinases belonging to the JNK family have been identi®ed (Gupta et al, 1996). Immunoprecipitation with anti-JNK1 antibodies and transient expression of an epitope-tagged JNK1 construct demonstrated that JNK1 is at least one of the JNKfamily members activated by Ret.…”

Section: Discussionmentioning

confidence: 99%

Signalling of the Ret receptor tyrosine kinase through the c-Jun NH2-terminal protein kinases (JNKs): evidence for a divergence of the ERKs and JNKs pathways induced by Ret

et al. 1998

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The RET proto-oncogene encodes a functional receptor tyrosine kinase (Ret) for the Glial cell line Derived Neurotrophic Factor (GDNF). RET is involved in several neoplastic and non-neoplastic human diseases. Oncogenic activation of RET is detected in human papillary thyroid tumours and in multiple endocrine neoplasia type 2 syndromes. Inactivating mutations of RET have been associated to the congenital megacolon, i.e. Hirschprung's disease. In order to identify pathways that are relevant for Ret signalling to the nucleus, we have investigated its ability to induce the c-Jun NH 2 -terminal protein kinases (JNK). Here we show that triggering the endogenous Ret, expressed in PC12 cells, induces JNK activity; moreover, Ret is able to activate JNK either when transiently transfected in COS-1 cells or when stably expressed in NIH3T3 ®broblasts or in PC Cl 3 epithelial thyroid cells. JNK activation is dependent on the Ret kinase function, as a kinase-de®cient RET mutant, associated with Hirschsprung's disease, fails to activate JNK. The pathway leading to the activation of JNK by RET is clearly divergent from that leading to the activation of ERK: substitution of the tyrosine 1062 of Ret, the Shc binding site, for phenylalanine abrogates ERK but not JNK activation. Experiments conducted with dominant negative mutants or with negative regulators demonstrate that JNK activation by Ret is mediated by Rho/Rac related small GTPases and, particularly, by Cdc42.

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Section: Discussionmentioning

confidence: 99%

Signalling of the Ret receptor tyrosine kinase through the c-Jun NH2-terminal protein kinases (JNKs): evidence for a divergence of the ERKs and JNKs pathways induced by Ret

et al. 1998

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“…In the JNK subgroup, three genes (jnk1, jnk2 and jnk3) and ten di erent splicing variants have been described (Gupta et al, 1996;Widmann et al, 1999). 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.…”

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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“…Very recently, Gupta et al showed that both c-Jun and ATF-2 bind to and are phosphorylated by JNK, while JunB binds to but is not phosphorylated by JNK, and Elk-1 does not bind to but is phosphorylated by JNK, suggesting that the binding and phosphorylation may be distinct attributes of the interaction between JNKs and their target proteins (Gupta et al, 1996). Thus, it can be speculated that the binding of BCL-6 with MAPK may also play multiple roles besides phosphorylation.…”

Section: Phosphorylation Of Bcl-6 By Mapk In Vivo M Moriyama Et Almentioning

confidence: 99%

BCL-6 is phosphorylated at multiple sites in its serine- and proline-clustered region by mitogen-activated protein kinase (MAPK) in vivo

et al. 1997

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BCL-6 gene alterations have been observed in 27 ± 45% of di use large B-cell lymphomas (DLBs) with chromosomal translocations at 3q27. The deregulated expression of normal BCL-6 protein caused by this chromosomal translocation is believed to be responsible for lymphomagenesis. Recently, we demonstrated that BCL-6 is expressed at high levels in germinal center B-cells as a 92-98 kDa nuclear protein in a constitutively phosphorylated form. In this study, we show that BCL-6 is phosphorylated by mitogen-activated protein kinase (MAPK) in vitro at the sites phosphorylated in vivo. These numerous phosphorylation sites were found to be located in its serine-and proline-clustered (SPC) region (amino acids-250-483). BCL-6 phosphorylation signi®-cantly increased in Ramos cells following stimulation with 12-o-tetradecanoylphorbol-13-acetate (TPA) or BCL-6-and erk1-transfected COS-7 cells stimulated with epidermal growth factor (EGF), and the increase of phosphorylation was inhibited by MEK1 inhibitor, PD98059. Furthermore, we observed that BCL-6 was associated with MAPK in vivo and its SPC region was important for this association. These results suggest that the functions of BCL-6 are regulated by phosphorylation mediated by the MAPK signaling pathway.

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Selective interaction of JNK protein kinase isoforms with transcription factors.

Abstract: The JNK protein kinase is a member of the MAP kinase group that is activated in response to dual phosphorylation on threonine and tyrosine. Ten

Cited by 1,249 publications

References 53 publications

Signalling of the Ret receptor tyrosine kinase through the c-Jun NH2-terminal protein kinases (JNKs): evidence for a divergence of the ERKs and JNKs pathways induced by Ret

Signalling of the Ret receptor tyrosine kinase through the c-Jun NH2-terminal protein kinases (JNKs): evidence for a divergence of the ERKs and JNKs pathways induced by Ret

From receptors to stress-activated MAP kinases

BCL-6 is phosphorylated at multiple sites in its serine- and proline-clustered region by mitogen-activated protein kinase (MAPK) in vivo

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