caa a22 4500 378884050 CHVBK 20180305123438.0 cr unu---uuuuu 161128e20040901xx s 000 0 eng 10.1515/BC.2004.105 doi (NATIONALLICENCE)gruyter-10.1515/BC.2004.105 Non-muscle α-actinin-4 interacts with plasminogen activator inhibitor type-1 (PAI-1) [Elektronische Daten] [Ulla Magdolen, Florian Schroeck, Sabine Creutzburg, Manfred Schmitt, Viktor Magdolen] PAI-1 modulates many biological processes involving fibrinolysis, cell migration or tissue remodelling. In addition to inhibiting serine proteases (mainly tPA and uPA), PAI-1 interacts with vitronectin (Vn), fibrin or α(1)-acid glycoprotein, interactions which are important for PAI-1-mediated effects in inflammation, tumor invasion and metastasis. To further identify proteins interacting with PAI-1, the yeast two-hybrid strategy was employed. Screening of a human placenta cDNA library identified - in addition to the C-terminal region of cytokeratin 18 (CK18182-430) - a large C-terminal fragment of α-actinin-4 (Act-4) as a binding partner for PAI-1. Two different cDNA clones encoding Act-4287-911 and Act-4330-911, respectively, were isolated. An Act-4330-911/GST-fusion protein, but not GST alone, was immunoprecipitated together with active PAI-1. In solid phase binding assays, active wild-type PAI-1 as well as the PAI-1 variant Q123K (which does not interact with multimeric Vn) was found to bind to Act-4330-911/GST. Latent PAI-1, latent Q123K, and the inactive PAI-1 variant Q55P did not display any binding activity. Act-4 is mainly present intracellularly and is involved in cellular motility via interaction with the actin cytoskeleton, thus probably affecting the metastatic potential of tumor cells. However, an extracellular Act-4-derived fragment (mactinin) has previously been identified, which (i) is generated by proteolytic action of uPA, (ii) displays significant chemotactic activity for monocytes, and (iii) promotes monocyte/macrophage maturation. We suggest that PAI-1, via interaction with both Act-4 and uPA, may function as a modulator of this mononuclear phagocyte response, not only in inflammation but also in tumor invasion and metastasis. © Walter de Gruyter Biochemistry nationallicence Molecular biology nationallicence Cellular biology nationallicence α-actinin nationallicence plasminogen activator inhibitor type 1 nationallicence yeast two-hybrid system nationallicence Magdolen Ulla Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany aut Schroeck Florian Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany aut Creutzburg Sabine Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany aut Schmitt Manfred Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany aut Magdolen Viktor Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany aut Biological Chemistry Walter de Gruyter 385/9(2004-09-01), 801-808 1431-6730 385:9<801 2004 385 bchm https://doi.org/10.1515/BC.2004.105 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/BC.2004.105 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Magdolen Ulla Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany aut NATIONALLICENCE 700 1- Schroeck Florian Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany aut NATIONALLICENCE 700 1- Creutzburg Sabine Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany aut NATIONALLICENCE 700 1- Schmitt Manfred Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany aut NATIONALLICENCE 700 1- Magdolen Viktor Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany aut NATIONALLICENCE 773 0- Biological Chemistry Walter de Gruyter 385/9(2004-09-01), 801-808 1431-6730 385:9<801 2004 385 bchm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter