Recent evidence indicates that the epidermal growth factor (EGF) receptor mediates a branch of lysophosphatidic acid (LPA)-induced signal transduction pathways that activate mitogen-activated protein (MAP) kinase. However, it is unclear whether the intrinsic tyrosine kinase activity of EGF receptor is involved. We previously showed that reactive oxygen species (ROS) were involved in the LPA-stimulated MAP kinase pathway. Here, we identify tyrosine phosphorylation of EGF receptor as an LPA signaling step that requires ROS. To evaluate the role of the tyrosine kinase activity of EGF receptor in the LPA-stimulated MAP kinase pathway, we examined the effects of an EGF receptor-specific tyrosine kinase inhibitor, PD158780. PD158780 potently inhibited the LPA-stimulated MAP kinase kinase 1/2 (MKK1/2) activation and EGF receptor tyrosine phosphorylation in HeLa cells, while it had no detectable effect on c-Src kinase activity. PD158780 also inhibited LPA-induced MKK1/2 activation and DNA synthesis in NIH 3T3 cells. Furthermore, we compared LPA-stimulated MKK1/2 and MAP kinase activation, transcriptional activity of the c-fos promoter, and DNA synthesis in B82L cells, which lack endogenous EGF receptor, and B82L cells expressing kinase-defective or wild-type human EGF receptor. Results obtained from analysis of these cell lines suggest that the EGF receptor tyrosine kinase contributes to the LPA-stimulated MAP kinase activation, c-fos transcription, and mitogenesis. Lysophosphatidic acid (LPA)1 is a bioactive phospholipid present in serum. LPA concentrations in serum are normally in the range of 2-20 M (1), but higher concentrations have been reported (2). LPA induces cellular responses by binding to a specific cell surface receptor(s) that is coupled to G i , G q , and G 12/13 subfamilies of heterotrimeric G-proteins (1, 3). LPA rapidly activates the mitogen-activated protein (MAP) kinase cascade, consisting of Ras, Raf-1, MAP kinase kinase (MKK or MEK) 1 and MKK 2 (MKK1/2), and MAP kinases (also called ERKs) (4 -9). It has been observed that LPA, as well as other agonists of G protein-coupled receptors, induces tyrosine phosphorylation of several signaling proteins in diverse cell types (6, 10 -15). Activation of protein tyrosine kinases, such as Src and PYK2, by agonists of G protein-coupled receptors have been reported in certain cell types (15, 16), but not others (17). The LPA-stimulated MAP kinase pathway is sensitive to certain protein tyrosine kinase inhibitors such as genistein (6). 2These observations suggest that regulation of protein tyrosine phosphorylation is an important signaling mechanism of LPA and other agonists of G protein-coupled receptors.Recently, it was reported that LPA and some other agonists of G protein-coupled receptors stimulate tyrosine phosphorylation of the epidermal growth factor (EGF) receptor (14, 15). Expression of a truncated human EGF receptor lacking the cytoplasmic domain in Rat1 cells abrogated LPA-stimulated MAP kinase activation, suggesting that the EGF receptor mediates at ...

A wandering liver has been described throughout modern medical literature as a rare entity. During the last few years, an increasing number of cases have been reported associated with colonic volvulus. We report a 17-year-old with a hypermobile liver seen on multiple radiographs and CT. The intraoperative findings demonstrated the liver in its normal anatomic position. We suggest that this entity is more common than thought, and the rise in incidence is likely secondary to increased utilization of pre-operative imaging of patients with colonic obstruction. Increased suspicion might result in further increased incidence of this exceedingly rare entity.

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Knight et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.