Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2000, PMID: 10777559

Crk activation of JNK via C3G and R-Ras.

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