Proteomics-based discovery of a novel, structurally unique, and developmentally regulated plasminogen receptor, Plg-RKT, a major regulator of cell surface plasminogen activation.
Activation of plasminogen, the zymogen of the primary thrombolytic enzyme, plasmin, is markedly promoted when plasminogen is bound to cell surfaces, arming cells with the broad spectrum proteolytic activity of plasmin. In addition to its role in thrombolysis, cell surface plasmin facilitates a wide array of physiologic and pathologic processes. Carboxypeptidase B-sensitive plasminogen binding sites promote plasminogen activation on eukaryotic cells. However, no integral membrane plasminogen receptors exposing carboxyl terminal basic residues on cell surfaces have been identified. Here we use the exquisite sensitivity of multidimensional protein identification technology and an inducible progenitor cell line to identify a novel differentiation-induced integral membrane plasminogen receptor that exposes a C-terminal lysine on the cell surface, Plg-R(KT) (C9orf46 homolog). Plg-R(KT) was highly colocalized on the cell surface with the urokinase receptor, uPAR. Our data suggest that Plg-R(KT) also interacts directly with tissue plasminogen activator. Furthermore, Plg-R(KT) markedly promoted cell surface plasminogen activation. Database searching revealed that Plg-R(KT) mRNA is broadly expressed by migratory cell types, including leukocytes, and breast cancer, leukemic, and neuronal cells. This structurally unique plasminogen receptor represents a novel control point for regulating cell surface proteolysis.
Andronicos
Nicholas M
NM
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Chen
Emily I
EI
Baik
Nagyung
N
Bai
Hongdong
H
Parmer
Caitlin M
CM
Kiosses
William B
WB
Kamps
Mark P
MP
Yates
John R
JR
Parmer
Robert J
RJ
Miles
Lindsey A
LA
D000595:Amino Acid Sequence; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003902:Detergents; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D017434:Protein Structure, Tertiary; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D003902:Detergents; D018398:Homeodomain Proteins; C548063:PLGRKT protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C097899:homeobox protein HOXA9; D016173:Macrophage Colony-Stimulating Factor; D010958:Plasminogen; D010959:Tissue Plasminogen Activator