Soluble urokinase receptor promotes cell adhesion and requires tyrosine-92 for activation of p56/59(hck).
The urokinase plasminogen activator receptor (uPAR) plays an important role in the migration of leukocytes. It occurs as a membrane-bound form that contains a glycosylphosphatidylinositol (GPI) anchor and also as a soluble form (suPAR) that lacks the GPI anchor. Recently, a sequence of amino acids, SRSRYLE, within the receptor has been found to become unmasked on uPA binding or chymotrypsin cleavage. Exposure of the epitope results in the activation of p56/p59(hck) kinase and chemotaxis of myelomonocytic cells. Using an epitope-tagged suPAR molecule, we found that both three-domain and two-domain suPAR promote the adhesion of differentiated THP-1 cells to fibronectin and vitronectin, indicating that suPAR can modify cell adhesion as well as cell migration. In addition, we found that the amino acid sequence RYLE, within the chemotactic peptide, is conserved across species and that alanine substitution of Tyr 92 decreased the ability of the peptide to activate p56/59(hck).
Trigwell
S
S
School of Biomedical Sciences, Queens Medical Centre, University of Nottingham, Nottingham, NG7 2UH, United Kingdom.
Wood
L
L
Jones
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology*; D002630:Chemotactic Factors / Q000378:metabolism / Q000494:pharmacology; D002918:Chymotrypsin / Q000378:metabolism; D017931:DNA Primers; D004789:Enzyme Activation / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D014443:Tyrosine / Q000502:physiology*
D002630:Chemotactic Factors; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014443:Tyrosine; D011494:Protein Kinases; D002918:Chymotrypsin