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Article: Induction of oocyte maturation by jun-N-terminal kinase (JNK) on the oncogenic ras-p21 pathway is dependent on the raf-MEK signal transduction pathway

TitleInduction of oocyte maturation by jun-N-terminal kinase (JNK) on the oncogenic ras-p21 pathway is dependent on the raf-MEK signal transduction pathway
Authors
Issue Date2000
PublisherSpringer. The Journal's web site is located at http://www.springer.com/medicine/oncology/journal/280
Citation
Cancer Chemotherapy And Pharmacology, 2000, v. 45 n. 6, p. 441-449 How to Cite?
AbstractPurpose: We have previously found that microinjection of activated MEK (mitogen activated kinase kinase) and ERK (mitogen-activated protein; MAP kinase) fails to induce oocyte maturation, but that maturation, induced by oncogenic ras-p21 and insulin-activated cell ras-p21, is blocked by peptides from the ras-binding domain of raf. We also found that jun kinase (JNK), on the stress-activated protein (SAP) pathway, which is critical to the oncogenic ras-p21 signal transduction pathway, is a strong inducer of oocyte maturation. Our purpose in this study was to determine the role of the raf- MEK-MAP kinase pathway in oocyte maturation and how it interacts with JNK from the SAP pathway. Methods: We microinjected raf dominant negative mutant mRNA (DN-raf) and the MEK-specific phosphatase, MKP-T4, either together with oncogenic p21 or c-raf mRNA, into oocytes or into oocytes incubated with insulin to determine the effects of these raf-MEK-MAP kinase pathway inhibitors. Results: We found that oocyte maturation induced by both oncogenic and activated normal p21 is inhibited by both DN-raf and by MKP-T4. The latter more strongly blocks the oncogenic pathway. Also an mRNA encoding a constitutively activated MEK strongly induces oocyte maturation that is not inhibited by DN-raf or by MKP-T4. Surprisingly, we found that oocyte maturation induced by JNK is blocked both by DN-raf and MKP-T4. Furthermore, we discovered that c-raf induces oocyte maturation that is inhibited by glutathione-S-transferase (GST), which we have found to be a potent and selective inhibitor of JNK. Conclusion: We conclude that there is a strong reciprocal interaction between the SAP pathway involving JNK and the raf-MEK- MAP kinase pathway and that oncogenic ras-p21 can be preferentially inhibited by MEK inhibitors. The results imply that blockade of both MEK and JNK- oncogenic ras-p21 interactions may constitute selective synergistic combination chemotherapy against oncogenic ras-induced tumors.
Persistent Identifierhttp://hdl.handle.net/10722/167644
ISSN
2015 Impact Factor: 2.824
2015 SCImago Journal Rankings: 1.283
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChie, Len_US
dc.contributor.authorAmar, Sen_US
dc.contributor.authorKung, HFen_US
dc.contributor.authorLin, MCMen_US
dc.contributor.authorChen, Hen_US
dc.contributor.authorChung, DLen_US
dc.contributor.authorAdler, Ven_US
dc.contributor.authorRonai, Zen_US
dc.contributor.authorFriedman, FKen_US
dc.contributor.authorRobinson, RCen_US
dc.contributor.authorKovac, Cen_US
dc.contributor.authorBrandtRauf, PWen_US
dc.contributor.authorYamaizumi, Zen_US
dc.contributor.authorMichl, Jen_US
dc.contributor.authorPincus, MRen_US
dc.date.accessioned2012-10-08T03:09:24Z-
dc.date.available2012-10-08T03:09:24Z-
dc.date.issued2000en_US
dc.identifier.citationCancer Chemotherapy And Pharmacology, 2000, v. 45 n. 6, p. 441-449en_US
dc.identifier.issn0344-5704en_US
dc.identifier.urihttp://hdl.handle.net/10722/167644-
dc.description.abstractPurpose: We have previously found that microinjection of activated MEK (mitogen activated kinase kinase) and ERK (mitogen-activated protein; MAP kinase) fails to induce oocyte maturation, but that maturation, induced by oncogenic ras-p21 and insulin-activated cell ras-p21, is blocked by peptides from the ras-binding domain of raf. We also found that jun kinase (JNK), on the stress-activated protein (SAP) pathway, which is critical to the oncogenic ras-p21 signal transduction pathway, is a strong inducer of oocyte maturation. Our purpose in this study was to determine the role of the raf- MEK-MAP kinase pathway in oocyte maturation and how it interacts with JNK from the SAP pathway. Methods: We microinjected raf dominant negative mutant mRNA (DN-raf) and the MEK-specific phosphatase, MKP-T4, either together with oncogenic p21 or c-raf mRNA, into oocytes or into oocytes incubated with insulin to determine the effects of these raf-MEK-MAP kinase pathway inhibitors. Results: We found that oocyte maturation induced by both oncogenic and activated normal p21 is inhibited by both DN-raf and by MKP-T4. The latter more strongly blocks the oncogenic pathway. Also an mRNA encoding a constitutively activated MEK strongly induces oocyte maturation that is not inhibited by DN-raf or by MKP-T4. Surprisingly, we found that oocyte maturation induced by JNK is blocked both by DN-raf and MKP-T4. Furthermore, we discovered that c-raf induces oocyte maturation that is inhibited by glutathione-S-transferase (GST), which we have found to be a potent and selective inhibitor of JNK. Conclusion: We conclude that there is a strong reciprocal interaction between the SAP pathway involving JNK and the raf-MEK- MAP kinase pathway and that oncogenic ras-p21 can be preferentially inhibited by MEK inhibitors. The results imply that blockade of both MEK and JNK- oncogenic ras-p21 interactions may constitute selective synergistic combination chemotherapy against oncogenic ras-induced tumors.en_US
dc.languageengen_US
dc.publisherSpringer. The Journal's web site is located at http://www.springer.com/medicine/oncology/journal/280en_US
dc.relation.ispartofCancer Chemotherapy and Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshFemaleen_US
dc.subject.meshJnk Mitogen-Activated Protein Kinasesen_US
dc.subject.meshMitogen-Activated Protein Kinases - Metabolismen_US
dc.subject.meshModels, Biologicalen_US
dc.subject.meshOocytes - Growth & Developmenten_US
dc.subject.meshProtein-Serine-Threonine Kinases - Metabolismen_US
dc.subject.meshProto-Oncogene Proteins C-Raf - Metabolismen_US
dc.subject.meshProto-Oncogene Proteins P21(Ras) - Physiologyen_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshXenopus Laevisen_US
dc.titleInduction of oocyte maturation by jun-N-terminal kinase (JNK) on the oncogenic ras-p21 pathway is dependent on the raf-MEK signal transduction pathwayen_US
dc.typeArticleen_US
dc.identifier.emailLin, MCM:mcllin@hkucc.hku.hken_US
dc.identifier.authorityLin, MCM=rp00746en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1007/s002800051017en_US
dc.identifier.pmid10854130-
dc.identifier.scopuseid_2-s2.0-0034033611en_US
dc.identifier.hkuros60691-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034033611&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume45en_US
dc.identifier.issue6en_US
dc.identifier.spage441en_US
dc.identifier.epage449en_US
dc.identifier.isiWOS:000087455900002-
dc.publisher.placeGermanyen_US
dc.identifier.scopusauthoridChie, L=6602998028en_US
dc.identifier.scopusauthoridAmar, S=35585899100en_US
dc.identifier.scopusauthoridKung, HF=7402514190en_US
dc.identifier.scopusauthoridLin, MCM=7404816359en_US
dc.identifier.scopusauthoridChen, H=7501625999en_US
dc.identifier.scopusauthoridChung, DL=7401719222en_US
dc.identifier.scopusauthoridAdler, V=7006627330en_US
dc.identifier.scopusauthoridRonai, Z=7102266349en_US
dc.identifier.scopusauthoridFriedman, FK=7101617312en_US
dc.identifier.scopusauthoridRobinson, RC=7403880279en_US
dc.identifier.scopusauthoridKovac, C=7003365001en_US
dc.identifier.scopusauthoridBrandtRauf, PW=7004376549en_US
dc.identifier.scopusauthoridYamaizumi, Z=7003596470en_US
dc.identifier.scopusauthoridMichl, J=35484894400en_US
dc.identifier.scopusauthoridPincus, MR=7101995825en_US

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