PMA-INDUCED DOWN-REGULATION OF THE RECEPTOR FOR ALPHA-2-MACROGLOBULININ HUMAN U937 CELLS

Transcription and expression of the urokinase (uPA) receptor (uPAR) ar e strongly stimulated by PMA. As for uPAR, the expression of alpha 2-M R is regulated by PMA in U937 cells. Ligand blotting experiments with the 39 kDa receptor-associated protein RAP, a ligand for alpha 2-MR, i ndicated that alpha 2-MR levels first increased and then decreased aft er PMA treatment. FACscan as well as immunoblotting analysis with alph a 2-MR-specific antibodies showed an identical trend: alpha 2-MR level s increased within the first day of treatment with PMA, decreased at l ater times, and totally disappeared by three days of treatment. The ef fect of PMA was not due to transcriptional down-regulation, as the alp ha 2-MR mRNA level did not decrease at later times. Sensitivity of U93 7 cells to uPA-saporin, a toxin conjugate that reguires binding to uPA R for killing activity, was also markedly decreased. These results sug gest that uPAR-mediated endocytosis depends on alpha 2-MR expression.