| First Author | Fredriksson L | Year | 2004 |
| Journal | EMBO J | Volume | 23 |
| Issue | 19 | Pages | 3793-802 |
| PubMed ID | 15372073 | Mgi Jnum | J:93392 |
| Mgi Id | MGI:3056973 | Doi | 10.1038/sj.emboj.7600397 |
| Citation | Fredriksson L, et al. (2004) Tissue plasminogen activator is a potent activator of PDGF-CC. EMBO J 23(19):3793-802 |
| abstractText | Tissue plasminogen activator (tPA) is a serine protease involved in the degradation of blood clots through the activation of plasminogen to plasmin. Here we report on the identification of tPA as a specific protease able to activate platelet-derived growth factor C (PDGF-C). The newly identified PDGF-C is secreted as a latent dimeric factor (PDGF-CC) that upon proteolytic removal of the N-terminal CUB domains becomes a PDGF receptor alpha agonist. The CUB domains in PDGF-CC directly interact with tPA, and fibroblasts from tPA-deficient mice fail to activate latent PDGF-CC. We further demonstrate that growth of primary fibroblasts in culture is dependent on a tPA-mediated cleavage of latent PDGF-CC, generating a growth stimulatory loop. Immunohistochemical analysis showed similar expression patterns of PDGF-C and tPA in developing mouse embryos and in tumors, indicating both autocrine and paracrine modes of activation of PDGF receptor-mediated signaling pathways. The identification of tPA as an activator of PDGF signaling establishes a novel role for the protease in normal and pathological tissue growth and maintenance, distinct from its well-known role in plasminogen activation and fibrinolysis. |
