Post-transcriptional regulation of the transferrin receptor and 4F2 antigen heavy chain mRNA during growth activation of spleen cells.

The expression of several cell surface proteins including the transferrin receptor and 4F2 antigen is induced when quiescent cells are activated and proliferate. We have studied this induction in mouse spleen cells after stimulation with 4 beta-phorbol 12-myristate 13-acetate (PMA), the Ca(2+)-ionophore, ionomycin and recombinant interleukin-2 (IL-2). The 4F2 antigen heavy chain and transferrin receptor mRNA were barely detectable in resting cells, but increased 60-fold within 4 h of growth stimulation. The corresponding proteins became measurable at the cell surface after 6 h, prior to the S phase. In run-on transcription assays the transferrin receptor gene was transcribed to almost the same extent in resting and growth-stimulated cell populations and the 4F2 antigen heavy chain gene was induced fivefold. This suggests that post-transcriptional control mechanisms are mainly responsible for the accumulation of the respective mRNA at the onset of cell proliferation. In the case of the transferrin receptor, the induction correlated with an activation of the mRNA-binding iron-regulatory factor which is known to increase the stability of the cytoplasmic transferrin receptor mRNA.