J Biol Chem 2000,
PMID: 10777559
Mochizuki, N; Ohba, Y; Kobayashi, S; Otsuka, N; Graybiel, A M; Tanaka, S; Matsuda, M
v-crk is an oncogene identified originally in CT10 chicken tumor virus. C3G, a guanine nucleotide exchange factor (GEF) for Rap1 and R-Ras, is postulated to transduce the oncogenic signal of v-Crk to c-Jun kinase (JNK). We have found that R-Ras, but not Rap1, mediates JNK activation by v-Crk in 293T and NIH 3T3 cells. Constitutively activated R-Ras, R-Ras(Val-38), but not Rap1(Val-12), activated JNK, as did the constitutively active H-Ras(Val-12) or Rac1(Val-12). v-Crk activation of JNK was inhibited by a dominant-negative mutant of R-Ras, R-Ras(Asn-43). JNK activation by R-Ras(Val-38) was inhibited by a dominant-negative mutant of mixed lineage kinase 3. Among six GEFs for Ras-family G proteins, mSos1, Ras-GRF, C3G, CalDAG-GEFI, Ras-GRP/CalDAG-GEFII, and Epac/cAMP-GEFI, GEFs for either H-Ras or R-Ras activated JNK and c-Jun-dependent transcription. CalDAG-GEFI and Epac/cAMP-GEFI, both of which are GEFs specific for Rap1, did not activate JNK or c-Jun-dependent transcription. These results demonstrate that R-Ras, but not Rap1, is the downstream effector of C3G to stimulate JNK. Finally, we found that expression of the dominant-negative R-Ras mutant induced flat reversion of NIH 3T3 cells transformed by v-Crk, suggesting that R-Ras-dependent JNK activation is critical for the transformation by v-Crk.
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Text Mining Data
Crk → R-Ras: "
Crk activation of JNK via C3G and
R-Ras
"
v-Crk → R-Ras: "
We have found that R-Ras , but not Rap1, mediates JNK activation by v-Crk in 293T and NIH 3T3 cells
"
v-Crk → Rap1: "
We have found that R-Ras, but not Rap1 , mediates JNK activation by v-Crk in 293T and NIH 3T3 cells
"
v-Crk ⊣ R-Ras: "
v-Crk activation of JNK was inhibited by a dominant negative mutant of R-Ras , R-Ras ( Asn-43 )
"
R-Ras ⊣ mixed lineage kinase 3: "
JNK activation by R-Ras ( Val-38 ) was inhibited by a dominant negative mutant of mixed lineage kinase 3
"
Manually curated Databases
-
Reactome Reaction:
TLN1
→
CRK
(reaction)
-
Reactome Reaction:
RAP1B
→
CRK
(reaction)
-
Reactome Reaction:
ITGA2B
→
CRK
(reaction)
-
Reactome Reaction:
RAP1B
→
CRK
(indirect_complex)
-
Reactome Reaction:
ITGB3
→
CRK
(indirect_complex)
-
Reactome Reaction:
FGB
→
CRK
(reaction)
-
Reactome Reaction:
ITGB3
→
CRK
(reaction)
-
Reactome Reaction:
PTK2
→
CRK
(indirect_complex)
-
Reactome Reaction:
APBB1IP
→
CRK
(reaction)
-
Reactome Reaction:
FN1
→
CRK
(reaction)
-
Reactome Reaction:
TLN1
→
CRK
(indirect_complex)
-
Reactome Reaction:
RAP1A
→
CRK
(reaction)
-
Reactome Reaction:
RAP1A
→
CRK
(indirect_complex)
-
Reactome Reaction:
BCAR1
→
CRK
(reaction)
-
Reactome Reaction:
SRC
→
CRK
(indirect_complex)
-
Reactome Reaction:
SRC
→
CRK
(reaction)
-
Reactome Reaction:
FN1
→
CRK
(indirect_complex)
-
Reactome Reaction:
FGA
→
CRK
(reaction)
-
Reactome Reaction:
FGG
→
CRK
(indirect_complex)
-
Reactome Reaction:
FGA
→
CRK
(indirect_complex)
-
Reactome Reaction:
FGG
→
CRK
(reaction)
-
Reactome Reaction:
FGB
→
CRK
(indirect_complex)
-
Reactome Reaction:
BCAR1
→
CRK
(indirect_complex)
-
Reactome Reaction:
VWF
→
CRK
(indirect_complex)
-
Reactome Reaction:
APBB1IP
→
CRK
(indirect_complex)
-
Reactome Reaction:
PTK2
→
CRK
(reaction)
-
Reactome Reaction:
VWF
→
CRK
(reaction)
-
Reactome Reaction:
ITGA2B
→
CRK
(indirect_complex)
-
WikiPathways Serotonin Receptor 2 and ELK-SRF/GATA4 signaling:
RASGRP1
→
HRAS/KRAS/NRAS
(mim-necessary-stimulation)
In total, 14 gene pairs are associated to this article in curated databases