PMA‐induced down‐regulation of the receptor for α2‐macroglobulin in human U937 cells

FEBS Letters

Sidenius, Nicolai²  Cavallaro, Ugo²  Conese, Massimo²  Blasi, Francesco²  Olson, David¹  Soria, Marco R.² 

[1]Microbiology Institute, University of Copenhagen, Copenhagen, Denmark

[2]Department of Biological and Technological Research, Istituto Scientifco H.S. Raffaele, and Department of Genetics and Microbial Biology, University of Milano, via Olgettina 60, 20132 Milan, Italy

关键词: Phorbol ester;    Urokinase receptor;    α2-Macroglobulin receptor;    Endocytosis;    α2-MR;    α2-macroglobulin receptor/low density lipoprotein receptor-related protein;    PAI-1;    plasminogen activator inhibitor type-1;    PMA;    tetradecanoyl-phorbol acetate;    RAP;    α2-macroglobulin receptor-associated protein;    SAP;    saporin;    uPA;    urokinase-type plasminogen activator;    uPAR;    urokinase-type plasminogen activator receptor;   

DOI  :  10.1016/0014-5793(94)01399-L

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Transcription and expression of the urokinase (uPA) receptor (uPAR) are strongly stimulated by PMA. As for uPAR, the expression of α2-MR is regulated by PMA in U937 cells. Ligand blotting experiments with the 39 kDa receptor-associated protein RAP, a ligand for α2-MR, indicated that α2-MR levels first increased and then decreased after PMA treatment. FACscan as well as immunoblotting analysis with α2-MR-specific antibodies showed an identical trend: α2-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 α2-MR mRNA level did not decrease at later times. Sensitivity of U937 cells to uPA-saporin, a toxin conjugate that reguires binding to WAR for killing activity, was also markedly decreased. These results suggest that uPAR-mediated endocytosis depends on α2-MR expression.

【 授权许可】

Unknown