PuSH - Publikationsserver des Helmholtz Zentrums München: Binding of urokinase plasminogen activator to gp130 via a putative urokinase-binding consensus sequence.

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Liang, O.D.* ; Chavakis, T.* ; Linder, M.* ; Bdeir, K.* ; Kuo, A.* ; Preissner, K.T.*

Binding of urokinase plasminogen activator to gp130 via a putative urokinase-binding consensus sequence.

Biol. Chem. 384, 229-236 (2003)

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Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.

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Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) are instrumental in cellular activities during inflammation, angiogenesis and tumor metastasis. Recent studies suggest that uPA might exert its function on cell proliferation and migration in a uPAR-independent manner or through an adaptor to the uPA-uPAR system. By applying phage display technology, we have identified a putative uPA-binding consensus sequence BXXSSXXB (where B represents a basic amino acid and X represents any amino acid), which has no apparent sequence correlation to uPAR. This uPA-binding motif apparently recognizes the kringle domain of the protease and has an agonistic effect on uPA binding to immobilized uPAR, thereby possibly serving as part of an adaptor component for uPAR signaling. As a result of protein database searches, this motif was found in the extracellular domain of several cell surface proteins, some of which were proposed to be associated with the uPA-uPAR system. Among these, gp130, a common signal transducer for cytokines, was identified as a uPA-binding protein. The specificity of this interaction was demonstrated by inhibition of uPA binding to immobilized gp130 with soluble gp130. Furthermore, the binding could be partially inhibited by a uPA-binding consensus sequence-containing fusion protein in a dose-dependent manner, with an IC50 of approximately 1 microM, indicating that the uPA-binding motif is apparently involved in the uPA-gp130 interaction. The association of gp130 with uPA may link the uPA-uPAR system to various signal transduction pathways.

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