Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Protein J
2004 Apr 01;233:235-8. doi: 10.1023/b:jopc.0000026419.54902.bb.
Show Gene links
Show Anatomy links
An effector peptide from glutathione-S-transferase-pi strongly and selectively blocks mitotic signaling by oncogenic ras-p21.
Chie L
,
Adler V
,
Friedman FK
,
Chung D
,
Pincus MR
.
Abstract
Oncogenic ras-p21 directly activates jun-N-terminal kinase (JNK) and its substrate, jun as a unique step on its mitogenic signal transduction pathway. This activation is blocked by the specific JNK-jun inhibitor, glutathione-S-transferase-pi (GST-pi). Four domains of GST-pi have been implicated in this regulatory function: 34-50, 99-121, 165-182, and 194-201. The 34-50 domain is unique in that it does not affect GST-pi binding to JNK-jun but blocks jun phosphorylation by JNK. We now find that it completely blocks oncogenic (Val 12-) ras-p21-induced oocyte maturation but has no effect on insulin-induced oocyte maturation. Because the latter process requires activation of wild-type ras-p21, this peptide appears to be specific for inhibiting only the oncogenic form of ras-p21, suggesting its use in treating ras-induced tumors.
Adler,
Activation of c-Jun-NH2-kinase by UV irradiation is dependent on p21ras.
1996, Pubmed
Adler,
Activation of c-Jun-NH2-kinase by UV irradiation is dependent on p21ras.
1996,
Pubmed
Adler,
Regulation of JNK signaling by GSTp.
1999,
Pubmed
Adler,
Effector peptides from glutathione-S-transferase-pi affect the activation of jun by jun-N-terminal kinase.
2004,
Pubmed
Adler,
Complexes of p21RAS with JUN N-terminal kinase and JUN proteins.
1995,
Pubmed
Amar,
Selective inhibition of oncogenic ras-p21 in vivo by agents that block its interaction with jun-N-kinase (JNK) and jun proteins. Implications for the design of selective chemotherapeutic agents.
1997,
Pubmed
,
Xenbase
Barbacid,
ras genes.
1987,
Pubmed
Birchmeier,
ras proteins can induce meiosis in Xenopus oocytes.
1985,
Pubmed
,
Xenbase
Chie,
Loop domain peptides from the SOS ras-guanine nucleotide exchange protein, identified from molecular dynamics calculations, strongly inhibit ras signaling.
2004,
Pubmed
,
Xenbase
Deshpande,
Insulin induction of Xenopus laevis oocyte maturation is inhibited by monoclonal antibody against p21 ras proteins.
1987,
Pubmed
,
Xenbase
Flatgaard,
Isozyme specificity of novel glutathione-S-transferase inhibitors.
1993,
Pubmed
Kanovsky,
Peptides designed from molecular modeling studies of the ras-p21 protein induce phenotypic reversion of a pancreatic carcinoma cell line but have no effect on normal pancreatic acinar cell growth.
2003,
Pubmed
Karin,
The regulation of AP-1 activity by mitogen-activated protein kinases.
1995,
Pubmed
Miura,
Synthesis and expression of a synthetic gene for the activated human c-Ha-ras protein.
1986,
Pubmed
Monaco,
Identification of a glutathione-S-transferase effector domain for inhibition of jun kinase, by molecular dynamics.
1999,
Pubmed
Ranginwale,
Differences in patterns of activation of MAP kinases induced by oncogenic ras-p21 and insulin in oocytes.
2001,
Pubmed
,
Xenbase
