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:3.1.1.79 (
hormone-sensitive lipase
)
2,163
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hormone-sensitive lipase (
EC 3.1.1.79
;
HSL
) is a key enzyme in the mobilization of fatty acids from stored triacylglycerols.
HSL
activity is controlled by phosphorylation of at least four serines. In rat
HSL
, Ser563, Ser659 and Ser660 are phosphorylated by protein kinase A (PKA) in vitro as well as in vivo, and Ser660 and Ser659 have been shown to be the activity-controlling sites in vitro. The exact molecular events of PKA-mediated activation of
HSL
in vitro are yet to be determined, but increases in both Vmax and S0.5 seem to be involved, as recently shown for human
HSL
. In this study, the hydrophobic fluorescent probe 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (bis-
ANS
) was found to inhibit the hydrolysis of triolein by purified recombinant rat adipocyte
HSL
, with a decrease in the effect of bis-
ANS
upon PKA phosphorylation of
HSL
. The interaction of
HSL
with bis-
ANS
was found to have a Kd of 1 microM in binding assays. Upon PKA phosphorylation, the interactions of
HSL
with both bis-
ANS
and the alternative probe SYPRO Orange were increased. By negative stain transmission electron microscopy, phosphorylated
HSL
was found to have a closer interaction with phospholipid vesicles than unphosphorylated
HSL
. Taken together, our results show that
HSL
increases its hydrophobic nature upon phosphorylation by PKA. This suggests that PKA phosphorylation induces a conformational change that increases the exposed hydrophobic surface and thereby facilitates binding of
HSL
to the lipid substrate.
...
PMID:Phosphorylation of hormone-sensitive lipase by protein kinase A in vitro promotes an increase in its hydrophobic surface area. 1966 63
