J Biol Chem 1995,
PMID: 8530511
Xie, Y; Pendergast, A M; Hung, M C
To clarify the role of the Shc-Grb2-Sos trimer in the oncogenic signaling of the point mutation-activated HER-2/neu receptor tyrosine kinase (named p185), we interfered with the protein-protein interactions in the Shc.Grb2.Sos complex by introducing Grb2 mutants with deletions in either amino- (delta N-Grb2) or carboxyl-(delta C-Grb2) terminal SH3 domains into B104-1-1 cells derived from NIH3T3 cells expressing the point mutation-activated HER-2/neu. We found that the transformed phenotypes of the B104-1-1 cells were largely reversed by the delta N-Grb2. The effect of the delta C-Grb2 was much weaker. Biochemical analysis showed that the delta N-Grb2 was able to associate Shc but not p185 or Sos, while the delta C-Grb2 bound to Shc, p185, and Sos. The p185-mediated Ras activation was severely inhibited by the delta N-Grb2 but not the delta C-Grb2. Taken together, these data demonstrate that interruption of the interaction between Shc and the endogenous Grb2 by the delta N-Grb2 impairs the oncogenic signaling of the activated p185, indicating that (i) the delta N-Grb2 functions as a strong dominant-negative mutant, and (ii) Shc/Grb2/Sos pathway plays a major role in mediating the oncogenic signal of the activated p185. Unlike the delta N-Grb2, delta C-Grb2 appears to be a relatively weak dominant-negative mutant, probably due to its ability to largely fulfill the biological functions of the wild-type Grb2.
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Text Mining Data
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Manually curated Databases
-
Reactome Reaction:
ERBB3
→
SOS1
(reaction)
-
Reactome Reaction:
GRB2
→
ERBB4
(reaction)
-
Reactome Reaction:
BTC
→
GRB2
(reaction)
-
Reactome Reaction:
NRAS
→
ERBB4
(reaction)
-
Reactome Reaction:
GRB2
→
KRAS
(reaction)
-
Reactome Reaction:
BTC
→
HRAS
(reaction)
-
Reactome Reaction:
EREG
→
GRB2
(indirect_complex)
-
Reactome Reaction:
KRAS
→
ERBB4
(reaction)
-
Reactome Reaction:
NRG2
→
KRAS
(reaction)
-
Reactome Reaction:
SHC1
→
SOS1
(indirect_complex)
-
Reactome Reaction:
BTC
→
GRB2
(indirect_complex)
-
Reactome Reaction:
GRB2
→
NRG1
(indirect_complex)
-
Reactome Reaction:
BTC
→
NRAS
(reaction)
-
Reactome Reaction:
SOS1
→
ERBB4
(reaction)
-
Reactome Reaction:
EGF
→
SOS1
(reaction)
-
Reactome Reaction:
EGFR
→
NRAS
(reaction)
-
Reactome Reaction:
EGF
→
HRAS
(reaction)
-
Reactome Reaction:
EGF
→
KRAS
(reaction)
-
Reactome Reaction:
BTC
→
SOS1
(indirect_complex)
-
Reactome Reaction:
EGFR
→
GRB2
(indirect_complex)
-
Reactome Reaction:
ERBB3
→
GRB2
(reaction)
-
Reactome Reaction:
KRAS
→
SHC1
(reaction)
-
Reactome Reaction:
HBEGF
→
HRAS
(reaction)
-
Reactome Reaction:
GRB2
→
NRG4
(reaction)
-
Reactome Reaction:
NRG4
→
KRAS
(reaction)
-
Reactome Reaction:
NRG2
→
SOS1
(reaction)
-
Reactome Reaction:
ERBB3
→
SOS1
(indirect_complex)
-
Reactome Reaction:
ERBB3
→
GRB2
(indirect_complex)
-
Reactome Reaction:
ERBB3
→
KRAS
(reaction)
-
Reactome Reaction:
EGFR
→
GRB2
(reaction)
-
Reactome Reaction:
HRAS
→
ERBB4
(reaction)
-
Reactome Reaction:
NRAS
→
NRG1
(reaction)
-
Reactome Reaction:
KRAS
→
SOS1
(reaction)
-
Reactome Reaction:
GRB2
→
SHC1
(indirect_complex)
-
Reactome Reaction:
HBEGF
→
SOS1
(reaction)
-
Reactome Reaction:
NRAS
→
SHC1
(reaction)
-
Reactome Reaction:
NRG2
→
NRAS
(reaction)
-
Reactome Reaction:
EREG
→
SOS1
(indirect_complex)
-
Reactome Reaction:
GRB2
→
NRG2
(indirect_complex)
-
Reactome Reaction:
EGF
→
GRB2
(reaction)
-
Reactome Reaction:
SOS1
→
ERBB4
(indirect_complex)
-
Reactome Reaction:
EGF
→
NRAS
(reaction)
-
Reactome Reaction:
EGFR
→
HRAS
(reaction)
-
Reactome Reaction:
GRB2
→
HBEGF
(indirect_complex)
-
Reactome Reaction:
ERBB2
→
NRAS
(reaction)
-
Reactome Reaction:
ERBB2
→
SOS1
(indirect_complex)
-
Reactome Reaction:
GRB2
→
NRAS
(reaction)
-
Reactome Reaction:
HRAS
→
SOS1
(reaction)
-
Reactome Reaction:
EREG
→
KRAS
(reaction)
-
Reactome Reaction:
NRAS
→
SOS1
(reaction)
-
Reactome Reaction:
SOS1
→
NRG1
(indirect_complex)
-
Reactome Reaction:
EREG
→
HRAS
(reaction)
-
Reactome Reaction:
HBEGF
→
NRAS
(reaction)
-
Reactome Reaction:
ERBB2
→
KRAS
(reaction)
-
Reactome Reaction:
BTC
→
KRAS
(reaction)
-
Reactome Reaction:
SHC1
→
SOS1
(reaction)
-
Reactome Reaction:
GRB2
→
NRG1
(reaction)
-
Reactome Reaction:
GRB2
→
NRG4
(indirect_complex)
-
Reactome Reaction:
GRB2
→
HBEGF
(reaction)
-
Reactome Reaction:
GRB2
→
ERBB4
(indirect_complex)
-
Reactome Reaction:
NRG2
→
HRAS
(reaction)
-
Reactome Reaction:
ERBB3
→
NRAS
(reaction)
-
Reactome Reaction:
EGFR
→
KRAS
(reaction)
-
Reactome Reaction:
ERBB2
→
GRB2
(indirect_complex)
-
Reactome Reaction:
HRAS
→
SHC1
(reaction)
-
Reactome Reaction:
GRB2
→
HRAS
(reaction)
-
Reactome Reaction:
HRAS
→
NRG1
(reaction)
-
Reactome Reaction:
EGFR
→
SOS1
(reaction)
-
Reactome Reaction:
ERBB2
→
HRAS
(reaction)
-
Reactome Reaction:
EREG
→
SOS1
(reaction)
-
Reactome Reaction:
ERBB2
→
SOS1
(reaction)
-
Reactome Reaction:
GRB2
→
NRG2
(reaction)
-
Reactome Reaction:
GRB2
→
SHC1
(reaction)
-
Reactome Reaction:
NRG4
→
NRAS
(reaction)
-
Reactome Reaction:
NRG4
→
HRAS
(reaction)
-
Reactome Reaction:
NRG2
→
SOS1
(indirect_complex)
-
Reactome Reaction:
BTC
→
SOS1
(reaction)
-
Reactome Reaction:
EGF
→
SOS1
(indirect_complex)
-
Reactome Reaction:
HBEGF
→
SOS1
(indirect_complex)
-
Reactome Reaction:
ERBB3
→
HRAS
(reaction)
-
Reactome Reaction:
KRAS
→
NRG1
(reaction)
-
Reactome Reaction:
NRG4
→
SOS1
(indirect_complex)
-
Reactome Reaction:
EGFR
→
SOS1
(indirect_complex)
-
Reactome Reaction:
EGF
→
GRB2
(indirect_complex)
-
Reactome Reaction:
SOS1
→
NRG1
(reaction)
-
Reactome Reaction:
EREG
→
NRAS
(reaction)
-
Reactome Reaction:
ERBB2
→
GRB2
(reaction)
-
Reactome Reaction:
HBEGF
→
KRAS
(reaction)
-
Reactome Reaction:
NRG4
→
SOS1
(reaction)
-
Reactome Reaction:
EREG
→
GRB2
(reaction)
In total, 66 gene pairs are associated to this article in curated databases