STIMULATION OF LOW-DENSITY-LIPOPROTEIN UPTAKE IN HEPG2 CELLS BY EPIDERMAL GROWTH-FACTOR VIA A TYROSINE KINASE-DEPENDENT, BUT PROTEIN KINASE-C-INDEPENDENT, MECHANISM
A. Graham et Lj. Russell, STIMULATION OF LOW-DENSITY-LIPOPROTEIN UPTAKE IN HEPG2 CELLS BY EPIDERMAL GROWTH-FACTOR VIA A TYROSINE KINASE-DEPENDENT, BUT PROTEIN KINASE-C-INDEPENDENT, MECHANISM, Biochemical journal, 298, 1994, pp. 579-584
Epidermal growth factor (EGF), a potent mitogenic polypeptide, stimula
ted the uptake and degradation of [H-3]sucrose-labelled low-density li
poprotein (LDL) by HepG2 cells. The increase in LDL uptake was prevent
ed by the presence of the tyrosine kinase inhibitor genistein. Activat
ion of protein kinase C with phorbol 12-myristate 13-acetate (PMA) als
o stimulated the uptake of [H-3]LDL by HepG2 cells. When EGF and PMA w
ere added together, PMA increased the response to EGF in an additive m
anner. The protein kinase C inhibitor Ro-31-8220 prevented the increas
e in LDL uptake caused by PMA, but did not affect EGF stimulation of L
DL uptake. Similarly, down-regulation of protein kinase C activity by
chronic treatment with PMA also did not affect the EGF stimulation of
LDL uptake. These results suggest that the EGF stimulation of LDL upta
ke and degradation by HepG2 cells is mediated by a tyrosine kinase-dep
endent, but protein kinase C-independent, mechanism.