EMBO J 2001,
PMID: 11707405
Nicholson, P R; Empereur, S; Glover, H R; Dilworth, S M
ShcA and Grb2 are crucial components in signalling by most tyrosine kinase-associated receptors. How ever, it is not clear whether Grb2 bound directly to the receptor is equivalent to Grb2 associated via ShcA. We have used signalling stimulated by the middle T-antigen (MT) of polyoma virus to address this question. The two known Grb2-binding sites from murine ShcA, 313Y and 239/240YY, could functionally replace the MT ShcA-interacting region in transformation assays using Rat2 fibroblasts. This demonstrates that signal output from membrane-bound ShcA requires only these two sequences and the ShcA-binding site in MT does not recruit other signalling molecules. Two standard Grb2-interacting sequences, either from the EGF receptor or the ShcA 313Y region, could not replace the requirement for ShcA binding to MT, indicating an enhanced role for the ShcA 239/240YY motif. Sos1 and the docking protein Gab1 are brought into the MT complex through Grb2 association and this may be more effective using the 239/240YY sequence.
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Text Mining Data
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Manually curated Databases
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IRef Hprd Interaction:
SHC1
—
GRB2
(in vivo)
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IRef Hprd Interaction:
SHC1
—
GRB2
(in vitro)
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Reactome Reaction:
GRB2
→
KIT
(indirect_complex)
-
Reactome Reaction:
GRB2
→
KIT
(reaction)
-
Reactome Reaction:
GRB2
→
LYN
(indirect_complex)
-
Reactome Reaction:
GRB2
→
PTPN11
(reaction)
-
Reactome Reaction:
FYN
→
GRB2
(reaction)
-
Reactome Reaction:
GRB2
→
KITLG
(reaction)
-
Reactome Reaction:
FYN
→
GRB2
(indirect_complex)
-
Reactome Reaction:
GRB2
→
YES1
(reaction)
-
Reactome Reaction:
GRB2
→
LCK
(indirect_complex)
-
Reactome Reaction:
GRB2
→
LCK
(reaction)
-
Reactome Reaction:
GRB2
→
SRC
(indirect_complex)
-
Reactome Reaction:
GRB2
→
PTPN11
(indirect_complex)
-
Reactome Reaction:
GRB2
→
SRC
(reaction)
-
Reactome Reaction:
GRB2
→
KITLG
(indirect_complex)
-
Reactome Reaction:
GRB2
→
YES1
(indirect_complex)
-
Reactome Reaction:
GRB2
→
LYN
(reaction)
In total, 9 gene pairs are associated to this article in curated databases