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: EC:2.7.13.3 (
histidine kinase
)
2,405
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
It is well known that
c-Src
has important roles in tumorigenesis. However, it remains unclear whether
c-Src
contributes to metabolic reprogramming. Here we find that
c-Src
can interact with and phosphorylate hexokinases
HK1
and HK2, the rate-limiting enzymes in glycolysis. Tyrosine phosphorylation dramatically increases their catalytic activity and thus enhances glycolysis. Mechanistically,
c-Src
phosphorylation of
HK1
at Tyr732 robustly decreases its K
m
and increases its V
max
by disrupting its dimer formation. Mutation in
c-Src
phosphorylation site of either
HK1
or HK2 remarkably abrogates the stimulating effects of
c-Src
on glycolysis, cell proliferation, migration, invasion, tumorigenesis and metastasis. Due to its lower K
m
for glucose,
HK1
rather than HK2 is required for tumour cell survival when glucose is scarce. Importantly,
HK1
-Y732 phosphorylation level remarkably correlates with the incidence and metastasis of various clinical cancers and may serve as a marker to predict metastasis risk of primary cancers.
...
PMID:c-Src phosphorylation and activation of hexokinase promotes tumorigenesis and metastasis. 2805 52
