Non-muscle α-actinin-4 interacts with plasminogen activator inhibitor type-1 (PAI-1)
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Ulla Magdolen
Abstract
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.
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Artikel in diesem Heft
- Tapasin and other chaperones: models of the MHC class I loading complex
- Expression analysis of BCL2L12, a new member of apoptosis-related genes, in colon cancer
- SR-A1, a member of the human pre-mRNA splicing factor family, and its expression in colon cancer progression
- RNA interference by small hairpin RNAs synthesised under control of the human 7S K RNA promoter
- Kinetic characterization of phenol and aniline derivates as substrates of peroxidase
- Non-muscle α-actinin-4 interacts with plasminogen activator inhibitor type-1 (PAI-1)
- Oxidative modification of low-density lipoprotein: lipid peroxidation by myeloperoxidase in the presence of nitrite
- An apoptotic inducer, aralin, is a novel type II ribosome-inactivating protein from Aralia elata
- Inhibition of inducible TNF-α expression by oxaspirodion, a novel spiro-compound from the ascomycete Chaetomium subspirale
- Inhibition of sequestration of human B2 bradykinin receptor by phenylarsine oxide or sucrose allows determination of a receptor affinity shift and ligand dissociation in intact cells
- Effects of short-term chemical ablation of the GIP receptor on insulin secretion, islet morphology and glucose homeostasis in mice
- Comprehensive analysis of metabolites in Corynebacterium glutamicum by gas chromatography/mass spectrometry