We demonstrate that LPA stimulates the production and secretion of fibrogenic peptides, PDGF-B and CTGF, by cultured kidney proximal tubule cells through a mechanism that transactivates TGF-β. TGF-β transactivation by LPA is mediated by LPA2 receptor signaling transduced by the G-protein, Gαq, and is dependent on αvβ6 integrin-dependent ...

Jul 21, 1998 · Inhibition of RTK activity abolished LPA-mediated RTK and Shc tyrosine phosphorylation as well as ERK activation. Our results document a cross-talk at the receptor level between a GPCR for LPA and at least two RTKs, PDGFR and EGFR.

Dec 1, 2019 · In L cells lacking EGFR, LPA-induced Shc and ERK activation are mediated by the platelet-derived growth factor receptor (PDGFR) and these responses are inhibited by a specific PDGFR antagonist, AG1296 (Herrlich et al., 1998).

Here we show that increasing the catalytic activity of LPP1 decreased the pertussis toxin-sensitive stimulation of fibroblast migration by LPA and an LPA-receptor agonist that could not be dephosphorylated. Conversely, knockdown of endogenous LPP1 activity increased LPA …

Jul 6, 2024 · Lung parenchymal hypoxia has emerged as a cardinal feature of idiopathic pulmonary fibrosis (IPF). Hypoxia promotes cancer cell invasion and metastasis through signaling that is dependent upon the lysophosphatidic acid (LPA) receptor, LPA 1 (LPAR1). Abundant data indicate that LPA 1-dependent signaling also enhances lung fibrogenesis in IPF. We ...

To our knowledge, this study provides the first evidence that LPA stimulates human PDLF wound healing responses and interacts positively with PDGF to regulate these actions. These results suggest that LPA and its receptors play important modulatory roles in PDLF regenerative biology.

We show that lysophosphatidic acid (LPA), a ubiquitous phospholipid that is increased at sites of injury and inflammation, signals through LPA2 receptors and Gαq proteins of cultured proximal tubule cells to transactivate latent TGF-β in a Rho/Rho-kinase …

In L cells lacking EGFR, LPA-induced Shc and ERK activation are mediated by the platelet-derived growth factor receptor (PDGFR) and these responses are inhibited by a specific PDGFR...

ligand-independent activation of RTKs (27-31). LPA, endo-thelin, or thrombin activate the epidermal growth factor receptor in Rat-1 cells in the absence of EGF. Inhibition of EGFR kinase activity leads to failure of these stimuli to activate ERK and cfos (31). We report here the GPCR-mediated ligand-independent activation of PDGFR.

Given the importance of LPA 1 and RTKs (PDGFR, FGFR, and VEGFR) for invadosome formation under hypoxic conditions, we sought to determine whether LPA 1 is involved in the hypoxic activation of PDGFR. PDGFRβ phosphorylation at Y751, a PI3K binding site, was increased by 1.6- and 1.7-fold in cells exposed to hypoxia for 30 and 120 min ...