Non-muscle α-actinin-4 interacts with plasminogen activator inhibitor type-1 (PAI-1)

Verfasser / Beitragende:
[Ulla Magdolen, Florian Schroeck, Sabine Creutzburg, Manfred Schmitt, Viktor Magdolen]
Ort, Verlag, Jahr:
2004
Enthalten in:
Biological Chemistry, 385/9(2004-09-01), 801-808
Format:
Artikel (online)
ID: 378884050
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024 7 0 |a 10.1515/BC.2004.105  |2 doi 
035 |a (NATIONALLICENCE)gruyter-10.1515/BC.2004.105 
245 0 0 |a Non-muscle α-actinin-4 interacts with plasminogen activator inhibitor type-1 (PAI-1)  |h [Elektronische Daten]  |c [Ulla Magdolen, Florian Schroeck, Sabine Creutzburg, Manfred Schmitt, Viktor Magdolen] 
520 3 |a 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. 
540 |a © Walter de Gruyter 
690 7 |a Biochemistry  |2 nationallicence 
690 7 |a Molecular biology  |2 nationallicence 
690 7 |a Cellular biology  |2 nationallicence 
690 7 |a α-actinin  |2 nationallicence 
690 7 |a plasminogen activator inhibitor type 1  |2 nationallicence 
690 7 |a yeast two-hybrid system  |2 nationallicence 
700 1 |a Magdolen  |D Ulla  |u Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany  |4 aut 
700 1 |a Schroeck  |D Florian  |u Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany  |4 aut 
700 1 |a Creutzburg  |D Sabine  |u Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany  |4 aut 
700 1 |a Schmitt  |D Manfred  |u Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany  |4 aut 
700 1 |a Magdolen  |D Viktor  |u Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger str. 22, D-81675 München, Germany  |4 aut 
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