PMA-induced down-regulation of the receptor for alpha 2-macroglobulin in human U937 cells.
Transcription and expression of the urokinase (uPA) receptor (uPAR) are strongly stimulated by PMA. As for uPAR, the expression of alpha 2-MR is regulated by PMA in U937 cells. Ligand blotting experiments with the 39 kDa receptor-associated protein RAP, a ligand for alpha 2-MR, indicated that alpha 2-MR levels first increased and then decreased after PMA treatment. FACscan as well as immunoblotting analysis with alpha 2-MR-specific antibodies showed an identical trend: alpha 2-MR levels increased within the first day of treatment with PMA, decreased at later times, and totally disappeared by three days of treatment. The effect of PMA was not due to transcriptional down-regulation, as the alpha 2-MR mRNA level did not decrease at later times. Sensitivity of U937 cells to uPA-saporin, a toxin conjugate that reguires binding to uPAR for killing activity, was also markedly decreased. These results suggest that uPAR-mediated endocytosis depends on alpha 2-MR expression.
Conese
M
M
Department of Biological and Technological Research, Istituto Scientificio H.S. Raffaele, Milan, Italy.
Cavallaro
U
U
Sidenius
N
N
Olson
D
D
Soria
M R
MR
Blasi
F
F
D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D000922:Immunotoxins; D026563:LDL-Receptor Related Protein-Associated Protein; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014118:Toxins, Biological / Q000633:toxicity; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D002352:Carrier Proteins; D006023:Glycoproteins; D000922:Immunotoxins; D026563:LDL-Receptor Related Protein-Associated Protein; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C524898:PLAUR protein, human; D010940:Plant Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D055293:Receptors, Urokinase Plasminogen Activator; D054789:Ribosome Inactivating Proteins, Type 1; D014118:Toxins, Biological; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D014568:Urokinase-Type Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate