Non-muscle α-actinin-4 interacts with plasminogen activator inhibitor type-1 (PAI-1)
Gespeichert in:
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)
Online Zugang:
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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 | |
| 773 | 0 | |t Biological Chemistry |d Walter de Gruyter |g 385/9(2004-09-01), 801-808 |x 1431-6730 |q 385:9<801 |1 2004 |2 385 |o bchm | |
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| 950 | |B NATIONALLICENCE |P 700 |E 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 | ||
| 950 | |B NATIONALLICENCE |P 700 |E 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 | ||
| 950 | |B NATIONALLICENCE |P 700 |E 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 | ||
| 950 | |B NATIONALLICENCE |P 700 |E 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 | ||
| 950 | |B NATIONALLICENCE |P 700 |E 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 | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Biological Chemistry |d Walter de Gruyter |g 385/9(2004-09-01), 801-808 |x 1431-6730 |q 385:9<801 |1 2004 |2 385 |o bchm | ||
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