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;233:229-34. doi: 10.1023/b:jopc.0000026418.82786.5e.
Show Gene links
Show Anatomy links
Loop domain peptides from the SOS ras-guanine nucleotide exchange protein, identified from molecular dynamics calculations, strongly inhibit ras signaling.
Chie L
,
Friedman FK
,
Duncan T
,
Chen JM
,
Chung D
,
Pincus M
.
???displayArticle.abstract???
In the accompanying paper, we found, using molecular dynamics calculations, four domains of the ras-specific SOS guanine nucleotide exchange protein (residues 589-601, 654-675, 746-761, and 980-989) that differ markedly in conformation when SOS is complexed with either oncogenic (Val 12-) ras-p21 or wild-type ras-p21. Three of these domains contain three crystallographically undefined loops that we modeled in these calculations, and one is a newly identified non-loop domain containing SOS residues 980-989. We have now synthesized peptides corresponding to these four domains and find that all of them block Val 12-ras-p21-induced oocyte maturation. All of them also block insulin-induced oocyte maturation, but two of these peptides, corresponding to SOS residues 589-601 and 980-989, block oncogenic ras to a significantly greater extent. These results suggest that SOS contains domains, including the three loop domains, that are important for ras signaling and that several of these domains can activate different pathways specific to oncogenic or wild-type ras-p21.
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,
Complexes of p21RAS with JUN N-terminal kinase and JUN proteins.
1995,
Pubmed
Birchmeier,
ras proteins can induce meiosis in Xenopus oocytes.
1985,
Pubmed
,
Xenbase
Boriack-Sjodin,
The structural basis of the activation of Ras by Sos.
1998,
Pubmed
Chardin,
Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2.
1993,
Pubmed
Chen,
Molecular dynamics analysis of the structures of ras-guanine nucleotide exchange protein (SOS) bound to wild-type and oncogenic ras-p21. Identification of effector domains of SOS.
1999,
Pubmed
Chen,
Molecular dynamics on complexes of ras-p21 and its inhibitor protein, rap-1A, bound to the ras-binding domain of the raf-p74 protein: identification of effector domains in the raf protein.
1997,
Pubmed
Chie,
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.
2000,
Pubmed
,
Xenbase
Chie,
Identification of the site of inhibition of oncogenic ras-p21-induced signal transduction by a peptide from a ras effector domain.
1999,
Pubmed
Chie,
Identification of the site of inhibition of mitogenic signaling by oncogenic ras-p21 by a ras effector peptide.
2002,
Pubmed
,
Xenbase
Chung,
Inhibition of oncogenic and activated wild-type ras-p21 protein-induced oocyte maturation by peptides from the ras-binding domain of the raf-p74 protein, identified from molecular dynamics calculations.
1997,
Pubmed
,
Xenbase
Chung,
Evidence that oocyte maturation induced by an oncogenic ras-p21 protein and insulin is mediated by overlapping yet distinct mechanisms.
1992,
Pubmed
,
Xenbase
Deshpande,
Insulin induction of Xenopus laevis oocyte maturation is inhibited by monoclonal antibody against p21 ras proteins.
1987,
Pubmed
,
Xenbase
Duncan,
Comparison of molecular dynamics averaged structures for complexes of normal and oncogenic ras-p21 with SOS nucleotide exchange protein, containing computed conformations for three crystallographically undefined domains, suggests a potential role of these domains in ras signaling.
2004,
Pubmed
Holt,
Insulin stimulation of a MEK-dependent but ERK-independent SOS protein kinase.
1996,
Pubmed
Miura,
Synthesis and expression of a synthetic gene for the activated human c-Ha-ras protein.
1986,
Pubmed
Ranginwale,
Differences in patterns of activation of MAP kinases induced by oncogenic ras-p21 and insulin in oocytes.
2001,
Pubmed
,
Xenbase
Way,
A protein kinase C inhibitor induces phenotypic reversion of ras-transformed pancreatic cancer cells and cooperatively blocks tumor cell proliferation with an anti- ras peptide.
2002,
Pubmed