Intermolecular contact regions in urokinase plasminogen activator receptor.
The glycolipid-anchored urokinase-type plasminogen activator receptor (uPAR) is engaged in various signal transduction events related to cell adhesion, migration and proliferation. In this study, using phage display and peptide array techniques, we have identified several intermolecular contact regions of uPAR. Phage-displayed uPAR fragments bound to immobilized soluble uPAR on magnetic beads, revealing that regions uPAR-(7-28) and uPAR-(60-91) in domain I, uPAR-(101-121) in domain II and uPAR-(240-260) in domain III are possible uPAR-uPAR contact sites. Using peptide array, two additional sites could be identified, uPAR-(51-59) in domain I and uPAR-(144-155) in domain II. The putative uPAR-uPAR interaction sites are different from the previously identified uPA-binding sites. Functionally, peptides uPAR-(84-95) and uPAR-(240-248) could partially inhibit differentiated human U937 monocyte adhesion to vitronectin in the presence of uPA, indicating that these two uPAR regions might be involved not only in uPAR-uPAR but also in uPAR-vitronectin interactions. We propose that multiple uPAR-uPAR ectodomain interactions contribute considerably to the regulation of various cellular functions of uPAR.
Liang
Olin D
OD
Institut für Biochemie, Fachbereich Humanmedizin, Justus-Liebig-Universität, Friedrichstr. 24, D-35392 Giessen, Germany. olin.d.liang@biochemie.med.uni-giessen.de
Bdeir
Khalil
K
Matz
Rachel L
RL
Chavakis
Triantafyllos
T
Preissner
Klaus T
KT
D000595:Amino Acid Sequence; D001665:Binding Sites; D019921:Biotinylation; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D016415:Sequence Alignment; D015398:Signal Transduction; D013379:Substrate Specificity; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000378:metabolism; D019096:Vitronectin / Q000502:physiology
C524898:PLAUR protein, human; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D019096:Vitronectin; D014568:Urokinase-Type Plasminogen Activator