Plasminogen receptors: the first quarter century

Abstract

The interaction of plasminogen with cell surfaces results in promotion of plasmin formation and retention on the cell surface. This results in arming cell surfaces with the broad-spectrum proteolytic activity of plasmin. Over the past quarter century, key functional consequences of the association of plasmin with the cell surface have been elucidated. Physiologic and pathophysiologic processes with plasmin-dependent cell migration as a central feature include inflammation, wound healing, oncogenesis, metastasis, myogenesis, and muscle regeneration. Cell surface plasmin also participates in neurite outgrowth and prohormone processing. Furthermore, plasmin-induced cell signaling also affects the functions of inflammatory cells, via production of cytokines, reactive oxygen species, and other mediators. Finally, plasminogen receptors regulate fibrinolysis. In this review, we highlight emerging data that shed light on longstanding controversies and raise new issues in the field. We focus on (1) the impact of the recent X-ray crystal structures of plasminogen and the development of antibodies that recognize cell-induced conformational changes in plasminogen on our understanding of the interaction of plasminogen with cells; (2) the relationship between apoptosis and plasminogen binding to cells; (3) the current status of our understanding of the molecular identity of plasminogen receptors and the discovery of a structurally unique novel plasminogen receptor, Plg-RKT; (4) the determinants of the interplay between distinct plasminogen receptors and cellular functions; and (5) new insights into the role of colocalization of plasminogen and plasminogen activator receptors on the cell surface.

Figure 1. Alignment of predicted amino acid sequences of mouse, human, rat, dog and cow orthologs of Plg-R_KT (a) and the structural model of Plg-R_KT (b) show high interspecies sequence homology

Green indicates amino acids within the predicted primary transmembrane helix. Orange indicates amino acids within the predicted secondary transmembrane helix. Red indicates basic amino acids. This research was originally published in Blood, Andronicos, N.M., Chen, E.I., Baik, N., Bai, H., Parmer, C.M., Kiosses, W.B., Kamps, M.P., Yates, J.R., III, Parmer, R.J., Miles, L.A., Proteomics-based discovery of a novel, structurally unique, and developmentally regulated plasminogen receptor, Plg-R_KT, a major regulator of cell surface plasminogen activation, Blood. 2010, 115: 1319–30.© the American Society of Hematology.