Interaction of urokinase‐type plasminogenactivator (u‐PA) with its cellular receptor (u‐PAR) induces phosphorylation on tyrosine of a 38 kDa protein

Abstract

We demonstrate by immunopreoipitation that u-PAR is associated with a 38 kDa protein that is phosphorylated on tyrosine after u-PA treatment of cells. As tyrosine phosphorylation is the hallmark of many signal transduction pathways that promote growth and differentiation, these data suggest that u-PA, besides its role as a regulatory protease, might act as a para-or autocrine hormone.

Induction of c‐fos gene expression by urokinase‐type plasminogen activator in human ovarian cancer cells

“…Gels were electroblotted onto nitrocellulose sheets which were subsequently blocked with 1% BSA or 30% FCS [5]. Autoradiography of radiolabelled proteins was performed at -70°C with dried polyacrylamide gels using Konica X-ray film.…”

“…Transfection and isolation of the recombinant virus was performed as described [l 11. Soluble U-PAR was produced by infection of u-PAR was purified from culture supernatants by &nity chrontatography on u-PA-Sepharose which was prepared as previously described [5]. The supernatant containing the expressed u-PAR was passed over u-PA-Sepharose in the presence of 1 M NaCl.…”

“…Whereas it is generally held that the receptor focuses u-PA activity in space and time 133, recent data indicate that u-PAR, after the binding of u-PA, might interact with other transmembrane proteins in order to transduce a signal [4]. We have shown recently that in histiocytic lymphoma cells (U937) u-PA acts as an effector by activating a protein tyrosine kinase [5]. The distal components of this signalling pathway, which might regulate cell proliferation, are u~nown, Likely candidates for such a role could be products of i~ediate early genes, which are essential for the stimulation of cell proliferation by growth factors [6].…”

Urokinase Receptor Is Associated with the Components of the JAK1/STAT1 Signaling Pathway and Leads to Activation of This Pathway upon Receptor Clustering in the Human Kidney Epithelial Tumor Cell Line TCL-598

“…In addition, binding of uPA to the specific receptor (uPAR) could induce numerous intracellular signaling events. These include serine phosphorylation of cytokeratins (6); tyrosine phosphorylation of a 38-kDa protein (7); association of uPAR with several tyrosine-kinases of the src family (p60 fyn , p53/ p56 lyn , p56/p59 hck , p59 fgr ) (8,9); ␤1, ␤2, and ␤3-integrins (8,10,11); mechanical coupling to the cytoskeleton (12); de novo synthesis of diacylglycerol (13); cAMP formation (14); activation of inositol phosphate turnover; induction of Ca 2ϩ influx; release of Ca 2ϩ from intracellular stores (15); and c-fos gene expression (16). uPAR was found to form stable complexes with integrins and modulate their signaling function in cell adhesion and migration (8,10).…”

Proteolytic mechanisms involved in the metastasis of human melanoma cells

“…Receptor phosphorylation is common to many signal transduction pathways that promote growth and differentiation, and although the uPAR itself is not phosphorylated upon binding uPA, recent evidence indicates that interaction of uPA with its receptor induces tyrosine phosphorylation of an associated 38 kD protein (54).…”