JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain

Dérijard, Benoı̂t; Hibi, Masahiko; Wu, I-Huan; Barrett, Tamera; Su, Bing; Deng, Tiliang; Karin, Michael; Davis, Roger J.

doi:10.1016/0092-8674(94)90380-8

Cited by 3,067 publications

(2,420 citation statements)

References 51 publications

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“…FAST and RICK (also known as RIP2) kinases are also implicated in Fas-mediated apoptosis (Tian et al, 1995;Inohara et al, 1998;McCarthy et al, 1998). Various apoptotic stimuli such as Fas, TNF-a, ceramide and stresses induce activation of c-Jun N-terminal kinase (JNK), also known as stress activated protein kinase (SAPK) (Hibi et al, 1993;Derijard et al, 1994;Verheij et al, 1996;Xia et al, 1995). This suggests the involvement of the JNK pathway in the apoptotic signaling.…”

Section: Introductionmentioning

confidence: 99%

Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity

et al. 1999

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We have identi®ed and characterized a new calcium/ calmodulin (Ca 2+ /CaM) dependent protein kinase termed death-associated protein kinase 2 (DAPK2) that contains an N-terminal protein kinase domain followed by a conserved CaM-binding domain with signi®cant homologies to those of DAP kinase, a protein kinase involved in apoptosis. DAPK2 mRNA is expressed abundantly in heart, lung and skeletal muscle. The mapping results indicated that DAPK2 is located in the central region of mouse chromosome 9. In vitro kinase assay revealed that DAPK2 is autophosphorylated and phosphorylates myosin light chain (MLC) as an exogenous substrate. DAPK2 binds directly to CaM and is activated in a Ca 2+ /CaM-dependent manner. A constitutively active DAPK2 mutant is generated by removal of the CaMbinding domain (DCaM). Treatment of agonists that elevate intracellular Ca 2+ -concentration led to the activation of DAPK2 and transfection studies revealed that DAPK2 is localized in the cytoplasm. Overexpression of DAPK2, but not the kinase negative mutant, signi®cantly induced the morphological changes characteristic of apoptosis. These results indicate that DAPK2 is an additional member of DAP kinase family involved in apoptotic signaling.

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Section: Introductionmentioning

confidence: 99%

Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity

et al. 1999

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“…The proteins (p21Ras) encoded by the ras genes (Harvey-ras/Ha-ras, Kirsten-ras/Ki-ras and N-ras) bind guanine nucleotides, possess an intrinsic GTPase activity and cycle between an active (GTP bound) form and an inactive (GDP bound) state (Barbacid, 1987). Activated p21Ras proteins stimulate a cascade of cytoplasmic protein kinases including Raf, MEK, MAPK (Mitogen Activated Protein Kinase) which in turn culminates in the phosphorylation of nuclear transcription factors resulting in transcriptional activation of growth-mediating genes (Bollag and McCormick, 1991;Boulton et al, 1991;de Vries-Smit et al, 1992;Dent et al, 1992;DeÂ rijard et al, 1994;Hibi et al, 1993;Howe et al, 1992;Kyriakis et al, 1992;Lowenstein et al, 1992;Wood et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Transformation by ras modifies AP1 composition and activity

et al. 1997

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The Ras proteins play a central role in regulating cell growth and their mutation can lead to abnormal proliferation. To analyse the potential link betwen AP1 activity, encoded by members of the jun and fos gene families, and Ras-mediated cellular transformation, we have studied several NIH3T3 clones which overexpress the Ha-Ras or Ki-Ras oncogenes. These transformed ®broblasts accumulated higher levels of cJun, JunB, Fra1 and Fra2 proteins relative to their normal counterparts. They also displayed increased AP1 DNA binding activity which was predominantly composed of cJun and Fra1 containing dimers. Following serum stimulation of Ras clones, the elevated levels of cJun and Fra1 remained steady, while the induction of JunB and Fra2 was partially attenuated. Moreover, deregulated Ras signaling resulted in a complete loss of the serum inducibility of cFos and FosB. Ectopic co-expression of cJun and Fra1 in NIH3T3 ®broblasts led to a transformed phenotype, attenuation of cFos serum inducibility, increased AP1 activity and Cyclin D1 accumulation, all characteristics of oncogenic Ras expressing cells. These results demonstrate that cJun and Fra1 are crucial mediators of the Ras-transformation process.

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“…Four groups of MAPKs have been identi®ed in mammalian cells; the extracellular signalregulated kinases (ERKs) (also referred to as p42/44 MAPK) (for review see Davis, 1993), the c-Jun Nterminal kinases/stress-activated protein kinases (JNK/ SAPKs) (DeÂ rijard et al, 1994;Kallunki et al, 1994;Kyriakis et al, 1994), p38/CSBP/RK/MPK2/MX12 (Han et al, 1994;Lee et al, 1995), and ERK5 (Lee et al, 1997., Abe et al, 1996. The mammalian ERKs are involved in growth factor-mediated activation and di erentiation of a variety of cells, and are activated by growth factors and mitogens such as epidermal growth factor (EGF), PDGF and insulin.…”

Section: Introductionmentioning

confidence: 99%

“…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). Furthermore, JNK/ SAPK activation requires phosphorylation at two residues, Thr-183 and Tyr-185 by the MAPK kinase 4 (MKK4, also called SEK1, MEK4 or JNKK/ SAPKK) Lin et al, 1995;Sanchez et al, 1994), a dual speci®city protein kinase.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 1999

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JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain

Cited by 3,067 publications

References 51 publications

Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity

Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity

Transformation by ras modifies AP1 composition and activity

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

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