Selective regulation of intrinsic membrane proteins in HepG2

The asialoglycoprotein receptor (ASGP-R) and insulin receptor (IR) are cell-surface glycoproteins whose activity varies with the state of cellular differentiation. Expression of ASGP-R, IR and an organic anion binding protein (OABP) was studied in HepG2 cells grown in minimal essential medium (MEM) supplemented with 10% fetal bovine serum (FBS), dialyzed FBS (dFBS) or serum from other species and corresponding to different physiological states of the liver. Cells grown in MEM-10% FBS maximally express ASGP-R and IR binding activity at confluence while OABP antigen appears independent of the state of cellular proliferation. Growth in dFBS reduces expression of ASGP-R and IR at confluence by 60-80% without altering OABP content, total cellular protein synthesis, or 3H-thymidine incorporation. Immunoblot of these cells reveals virtually no mature, 45 kDa ASGP-R, but a small amount of 36 kDa protein; metabolic labelling with 35S-methionine shows reduced synthesis of 45 kDa ASGP-R and absence of the 36 kDa antigen. Northern blot analysis of ASGP-R mRNA levels suggests post-translational regulation is affected. Normal expression of ASGP-R and IR are restored by addition of a 300-350 dalton fraction of FBS to medium