TYPE-1 PLASMINOGEN-ACTIVATOR INHIBITOR INDUCES MULTIMERIZATION OF PLASMA VITRONECTIN - A SUGGESTED MECHANISM FOR THE GENERATION OF THE TISSUE FORM OF VITRONECTIN IN-VIVO

Citation
D. Seiffert et Dj. Loskutoff, TYPE-1 PLASMINOGEN-ACTIVATOR INHIBITOR INDUCES MULTIMERIZATION OF PLASMA VITRONECTIN - A SUGGESTED MECHANISM FOR THE GENERATION OF THE TISSUE FORM OF VITRONECTIN IN-VIVO, The Journal of biological chemistry, 271(47), 1996, pp. 29644-29651
Citations number
38
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
271
Issue
47
Year of publication
1996
Pages
29644 - 29651
Database
ISI
SICI code
0021-9258(1996)271:47<29644:TPIIMO>2.0.ZU;2-2
Abstract
The conformation and degree of multimerization of vitronectin (Vn) app ears to be of critical importance for its functions, but little is kno wn about the underlying mechanisms that control Vn multimerization. We report that Vn secreted by cultured hepatoma cells is present as a mi xture of monomeric and multimeric forms. A single protein of M(r) 45,0 00 co-purified with hepatoma cell-derived Vn, which was immunologicall y identified as type 1 plasminogen activator inhibitor (PAI-1). The po ssibility that PAI-1 may modulate Vn multimerization was investigated. The addition of active PAI-1 to unfractionated plasma containing Vn m onomers resulted in the formation of covalently and noncovalently asso ciated Vn multimers and expression of conformationally sensitive epito pes. In contrast, inactive forms of PAI-1 did not efficiently induce V n multimerization and conformational change, Gel filtration analysis r evealed that Vn remained multimeric after dissociation from PAI-1. Vn multimers were also assembled using purified monomeric Vn and PAI-1, s uggesting that a plasma cofactor was not required to induce Vn multime rization. This study provides insights into physiological mechanism re sponsible for the generation of homomultimeric Vn, a multimeric form o f Vn that is not in complex with other proteins and which expresses a functional repertoire distinct from that of plasma Vn.