Va. Tkachuk et al., ATYPICAL LOW-DENSITY-LIPOPROTEIN BINDING-SITE THAT MAY MEDIATE LIPOPROTEIN-INDUCED SIGNAL-TRANSDUCTION, Molecular pharmacology, 46(6), 1994, pp. 1129-1137
The characteristics of low density lipoprotein (LDL) binding in quiesc
ent cultures of human vascular smooth muscle cells (VSMC) have been fu
rther investigated and compared with the characteristics of high affin
ity LDL binding in human fibroblasts [via the apolipoprotein (ape) B/E
receptor] and with the properties of LDL-induced phosphoinositide cat
abolism in VSMC. In VSMC the bulk of specific I-125-LDL binding occurs
at a low affinity site, several characteristics of which are distinct
from those of I-125-LDL binding to the apo B/E receptor in fibroblast
s. (a) The affinity of LDL binding in VSMC is 25-50 times lower than t
hat in fibroblasts (K-d approximate to 50 mu g/ml versus K-d approxima
te to 2 mu g/ml). (b) The kinetics of LDL association and dissociation
in VSMC are more rapid than those in fibroblasts. (c) In contrast to
apo B/E receptor-mediated binding of LDL in fibroblasts, binding of LD
L to VSMC is insensitive to heparin, chemical modification of lysine r
esidues, and chelation (with EDTA) of divalent cations. (d) Apo E-free
high density lipoprotein(3) displaces labeled LDL more effectively in
VSMC than in fibroblasts. (e) The ratio of bound/internalized LDL to
degraded LDL differs markedly between fibroblasts and VSMC. LDL-stimul
ated phosphoinositide catabolism in VSMC, which occurs with an activat
ion constant similar to the K-d for low affinity LDL binding, is insen
sitive to heparin, modification of lysine and arginine residues in LDL
, and chelation of divalent cations. Thus, the atypical low affinity r
eceptor in these cells may mediate the effects of LDL on signal transd
uction.