Physical association of uPAR with the alphaV integrin on the surface of human NK cells.
The urokinase-type plasminogen activator receptor (uPAR) serves as a receptor for urokinase plasminogen activator (uPA) and plays a role in invasion and migration of certain immune cells, including NK cells. Although uPAR is anchored to the plasma membrane via a glycosylphosphatidylinositol lipid moiety, we have previously shown that uPAR crosslinking results in MAP kinase signaling and increased integrin expression on the surface of the human NK cell line, YT. We report, herein, that the binding of uPA to uPAR also activates the MAP kinase signaling cascade. Furthermore, we show the physical association between uPAR and integrins on YT cells using cocapping and fluorescence microscopy. These results suggest that signaling initiated by either uPAR binding to uPA or by uPAR clustering may depend on the physical association of uPAR with integrins, a process that may be a prerequisite for NK cell accumulation within established tumor metastases during adoptive therapy.
Department of Molecular Biology and Immunology, Institute for Cancer Research, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107, USA.
Ginelle C
GC
Gellert
Ronald H
RH
Goldfarb
Richard P
RP
Kitson
D000117:Acetylglucosamine / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D039564:Integrin alphaV / Q000737:chemistry / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000201:enzymology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D039564:Integrin alphaV; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D020928:Mitogen-Activated Protein Kinases; D014568:Urokinase-Type Plasminogen Activator; D000117:Acetylglucosamine