Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P43146 (
tumour suppressor
)
5,935
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The
tumour suppressor
gene product
Mig-6
acts as an inhibitor of epidermal growth factor (EGF) signalling. However, its posttranslational modifications and regulatory mechanisms have not been elucidated. Here, we investigated the phosphorylation of human
Mig-6
and found that Chk1 phosphorylated
Mig-6
in vivo as well as in vitro. Moreover, EGF stimulation promoted phosphorylation of
Mig-6
without DNA damage and the phosphorylation was inhibited by depletion of Chk1. EGF also increased Ser280-phosphorylated Chk1, a cytoplasmic-tethering form, via PI3K pathway. Mass spectrometric analyses suggested that Ser 251 of
Mig-6
was a major phosphorylation site by Chk1 in vitro and in vivo. Substitution of Ser 251 to alanine increased inhibitory activity of
Mig-6
against EGF receptor (EGFR) activation. Moreover, EGF-dependent activation of EGFR and cell growth were inhibited by Chk1 depletion, and were rescued by co-depletion of
Mig-6
. Our results suggest that Chk1 phosphorylates
Mig-6
on Ser 251, resulting in the inhibition of
Mig-6
, and that Chk1 acts as a positive regulator of EGF signalling. This is a novel function of Chk1.
...
PMID:Chk1 phosphorylates the tumour suppressor Mig-6, regulating the activation of EGF signalling. 2250 24
