Chemotactic effect of urokinase plasminogen activator

A major role for mechanisms independent of its proteolytic or growth factor domains

A. A. Poliakov, S. A. Mukhina, Dmitry Traktuev, R. Sh Bibilashvily, Y. G. Gursky, M. M. Minashkin, V. V. Stepanova, V. A. Tkachuk

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Urokinase type plasminogen activator (uPA) converts plasminogen to plasmin and is highly chemotactic for many cell types. We examined, using recombinant wild type and mutated forms of uPA, the extent to which its proteolytic properties, its growth-like domain (GFD) and/or interactions with the specific receptor (uPAR) contribute to the chemotactic activity towards vascular smooth muscle cells (SMC). Recombinant wild type uPA (r-uPA) stimulated cell migration nearly 5.8-fold, inactive r-uPA with a mutation in the catalitic domain (r-uPA(H/Q)), 3-fold, uPA without growth factor like domain (r-uPA(GFD-)), 2.6-fold, and a form containing both mutations (r- uPA(H/Q, GFD-), 3.3-fold. All recombinant forms of uPA, wild type and those with mutations were equally and highly effective (IC50~20 nM) in displacing 125I-r-uPA bound to SMC. These results indicate that additional mechanisms, not dependent on uPA's proteolytic activity or the binding ability of its GFD to uPAR, are the major contributors to its chemotactic action on SMC.

Original languageEnglish (US)
Pages (from-to)939-951
Number of pages13
JournalJournal of Receptor and Signal Transduction Research
Volume19
Issue number6
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

Plasminogen Activators
Urokinase-Type Plasminogen Activator
Intercellular Signaling Peptides and Proteins
Smooth Muscle Myocytes
Muscle
Mutation
Plasminogen
Fibrinolysin
Vascular Smooth Muscle
Inhibitory Concentration 50
Cell Movement
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chemotactic effect of urokinase plasminogen activator : A major role for mechanisms independent of its proteolytic or growth factor domains. / Poliakov, A. A.; Mukhina, S. A.; Traktuev, Dmitry; Bibilashvily, R. Sh; Gursky, Y. G.; Minashkin, M. M.; Stepanova, V. V.; Tkachuk, V. A.

In: Journal of Receptor and Signal Transduction Research, Vol. 19, No. 6, 01.01.1999, p. 939-951.

Research output: Contribution to journalArticle

Poliakov, A. A. ; Mukhina, S. A. ; Traktuev, Dmitry ; Bibilashvily, R. Sh ; Gursky, Y. G. ; Minashkin, M. M. ; Stepanova, V. V. ; Tkachuk, V. A. / Chemotactic effect of urokinase plasminogen activator : A major role for mechanisms independent of its proteolytic or growth factor domains. In: Journal of Receptor and Signal Transduction Research. 1999 ; Vol. 19, No. 6. pp. 939-951.
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