Stimulation of low-density lipoprotein uptake in HepG2 cells by epidermal growth factor via a tyrosine kinase-dependent, but protein kinase C-independent, mechanism.
Epidermal growth factor (EGF), a potent mitogenic polypeptide, stimulated the uptake and degradation of [3H]sucrose-labelled low-density lipoprotein (LDL) by HepG2 cells. The increase in LDL uptake was prevented by the presence of the tyrosine kinase inhibitor genistein. Activation of protein kinase C with phorbol 12-myristate 13-acetate (PMA) also stimulated the uptake of [3H]LDL by HepG2 cells. When EGF and PMA were added together, PMA increased the response to EGF in an additive manner. The protein kinase C inhibitor Ro-31-8220 prevented the increase in LDL uptake caused by PMA, but did not affect EGF stimulation of LDL 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 uptake and degradation by HepG2 cells is mediated by a tyrosine kinase-dependent, but protein kinase C-independent, mechanism.
Graham
A
A
Department of Biochemical Sciences, Wellcome Research Laboratories, Beckenham, Kent, U.K.
Russell
L J
LJ
D000085:Acetates / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004951:Esterification; D019833:Genistein; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013395:Sucrose / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000085:Acetates; D007211:Indoles; D007529:Isoflavones; D008077:Lipoproteins, LDL; D013395:Sucrose; D004815:Epidermal Growth Factor; D002784:Cholesterol; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C064758:Ro 31-8220