Nature 1996,
PMID: 8596637
Daub, H; Weiss, F U; Wallasch, C; Ullrich, A
Transduction of a mitogenic signal from the cell membrane to the nucleus involves the adapter proteins SHC and Grb2, which mediate activation of the Ras/mitogen-activated protein (MAP) kinase pathway. In contrast to receptor tyrosine kinases (RTKs), the signalling steps leading to Ras/MAP kinase activation by G-protein-coupled receptors (GPCRs) are still poorly characterized but appear to include beta gamma subunits of heterotrimeric G-proteins and as-yet unidentified tyrosine kinases. We report here that the epidermal growth factor receptor (EGFR) and the neu oncoprotein become rapidly tyrosine-phosphorylated upon stimulation of Rat-1 cells with the GPCR agonists endothelin-1, lysophosphatic acid and thrombin, suggesting that there is an intracellular mechanism for transactivation. Specific inhibition of EGFR function by either the selective tyrphostin AG1478 or a dominant-negative EGFR mutant suppressed MAP kinase activation and strongly inhibited induction of fos gene expression and DNA synthesis. Our results demonstrate a role for RTKs as downstream mediators in GPCR mitogenic signalling and suggest a ligand-independent mechanism of RTK activation through intracellular signal crosstalk.
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Text Mining Data
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Manually curated Databases
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NCI Pathway Database EGFR-dependent Endothelin signaling events:
EGF/EGFR dimer/SHC/GRB2/SOS1 complex (EGF-EGFR-SHC1-GRB2-SOS1)
→
EGF/EGFR dimer/SHC complex (EGF-EGFR-SHC1)
(modification, collaborate)
Evidence: physical interaction, other species
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NCI Pathway Database EGFR-dependent Endothelin signaling events:
EGF/EGFR dimer/SHC/GRB2/SOS1 complex (EGF-EGFR-SHC1-GRB2-SOS1)
→
GRB2/SOS1 complex (GRB2-SOS1)
(modification, collaborate)
Evidence: physical interaction, other species
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NCI Pathway Database EGFR-dependent Endothelin signaling events:
EGF/EGFR dimer/SHC complex (EGF-EGFR-SHC1)
→
GRB2/SOS1 complex (GRB2-SOS1)
(modification, collaborate)
Evidence: physical interaction, other species
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NCI Pathway Database EGFR-dependent Endothelin signaling events:
EGF/EGFR dimer complex (EGF-EGFR)
→
EGF/EGFR complex (EGF-EGFR)
(modification, collaborate)
Evidence: physical interaction, other species
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NCI Pathway Database EGFR-dependent Endothelin signaling events:
EGF/EGFR dimer complex (EGF-EGFR)
→
EGF/EGFR dimer/SHC complex (EGF-EGFR-SHC1)
(modification, collaborate)
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NCI Pathway Database EGFR-dependent Endothelin signaling events:
EGF/EGFR dimer complex (EGF-EGFR)
→
SHC (SHC1)
(modification, collaborate)
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NCI Pathway Database EGFR-dependent Endothelin signaling events:
EGF/EGFR dimer/SHC complex (EGF-EGFR-SHC1)
→
SHC (SHC1)
(modification, collaborate)
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
None
→
None
(modification, collaborate)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
None
→
HRAS/GTP complex (HRAS)
(modification, collaborate)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
None
→
HRAS/GDP complex (HRAS)
(modification, collaborate)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
None
→
EGF/EGFR dimer/SHC/GRB2/SOS1 complex (EGF-EGFR-SHC1-GRB2-SOS1)
(modification, collaborate)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
None
→
HRAS/GTP complex (HRAS)
(modification, collaborate)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
None
→
HRAS/GDP complex (HRAS)
(modification, collaborate)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
HRAS/GTP complex (HRAS)
→
HRAS/GDP complex (HRAS)
(modification, collaborate)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
HRAS/GDP complex (HRAS)
→
EGF/EGFR dimer/SHC/GRB2/SOS1 complex (EGF-EGFR-SHC1-GRB2-SOS1)
(modification, collaborate)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
ETA receptor/Endothelin-1 complex (EDNRA-EDN1)
→
None
(modification, activates)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
ETA receptor/Endothelin-1 complex (EDNRA-EDN1)
→
EGFR (EGFR)
(modification, activates)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
ETA receptor/Endothelin-1 complex (EDNRA-EDN1)
→
EGF (EGF)
(modification, activates)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
ETA receptor/Endothelin-1 complex (EDNRA-EDN1)
→
EGF/EGFR complex (EGF-EGFR)
(modification, activates)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
None
→
EGFR (EGFR)
(modification, activates)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
None
→
EGF (EGF)
(modification, activates)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
None
→
EGF/EGFR complex (EGF-EGFR)
(modification, activates)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
EGFR (EGFR)
→
EGF (EGF)
(modification, collaborate)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
EGFR (EGFR)
→
EGF/EGFR complex (EGF-EGFR)
(modification, collaborate)
Evidence: mutant phenotype, other species
-
NCI Pathway Database EGFR-dependent Endothelin signaling events:
EGF (EGF)
→
EGF/EGFR complex (EGF-EGFR)
(modification, collaborate)
Evidence: mutant phenotype, other species
In total, 26 gene pairs are associated to this article in curated databases