REVIEW: Urokinase as a Multidomain Protein and Polyfunctional Cell Regulator

V. V. Stepanova^1* and V. A. Tkachuk^1,2

¹Russian Cardiology Research Center, Ministry of Health of Russian Federation, Cherepkovskaya ul. 15, Moscow, 121552 Russia; fax: (095) 414-6719; E-mail: V.Stepanova@cardio.ru

²School of Fundamental Medicine, Lomonosov Moscow State University, Moscow, 119899 Russia

^* To whom correspondence should be addressed.

Received July 23, 2001; Revision received October 12, 2001

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The urokinase type plasminogen activator (urokinase) plays a pivotal role in the regulation of cell adhesion and migration during tissue remodeling. Urokinase not only specifically cleaves plasminogen and converts it into plasmin but also activates intracellular signaling upon binding to certain receptors on the cell surface. The polyfunctional properties of this protein are associated with its three-domain structure as follows: the C-terminal proteolytic domain containing the serine protease active center, the central kringle domain, and the N-terminal domain homologous to epidermal growth factor. This review considers functional properties of urokinase and of its fragments generated on the cell surface as a result of proteolytic processing. This review will discuss the mechanisms of urokinase-mediated regulation of cellular function upon binding to membrane receptors.

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KEY WORDS: urokinase, adhesion, migration, tissue remodeling, endocytosis, intracellular signaling

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