Kim, SN Park, JG Lee, EB Kim, SS Yoo, YS 2024-01-21T14:37:47Z 2024-01-21T14:37:47Z 2021-09-04 2000-01 0730-2312 https://pubs.kist.re.kr/handle/201004/141707 Lysophosphatidic acid (LPA) is a lipid metabolite that induces the activation of mitogen-activated protein kinase (MAPK) through binding to the G protein-coupled receptor in a number of cell lines and cultures. Recent studies have revealed that LPA is able to rapidly induce the phosphorylation of MAPK through an epidermal growth factor EGF receptor-dependent pathway. We investigated the role of the EGF receptor in the signaling pathway initialed by LPA stimulation in nerve growth factor (NGF)-responsive PC12 cells well known to transiently retract their own neurites upon LPA stimulation. LPA-stimulated MAPK signaling was suppressed by the selective EGF receptor inhibitor and in the dominant negative mutant EGF receptor cell line. As in the EGF signaling pathway, the complex of EGF receptor with adapter proteins Shc and Sos was formed in response to LPA stimulation, suggesting there is an intracellular mechanism for transactivation. A neurite retraction assay was also performed to examine the role of the EGF receptor in PC12 cell differentiation, which related to the involvement of LPA-induced neurite retraction. These results suggest that the receptor tyrosine kinase can be activated in a ligand-independent manner through intracellular crosstalk between the signaling pathways. (C) 2000 Wiley-Liss, Inc. English WILEY-LISS PROTEIN-COUPLED RECEPTORS MAP KINASE ACTIVATION INDUCED NEURITE RETRACTION TYROSINE-KINASE EGF RECEPTOR MEDIATED ACTIVATION PATHWAY PHOSPHORYLATION BRADYKININ P21(RAS) Characterization of epidermal growth factor receptor function in lysophosphatidic acid signaling in PC12 cells Article 10.1002/(SICI)1097-4644(20000301)76:3<386::AID-JCB6>3.3.CO;2-0 1 JOURNAL OF CELLULAR BIOCHEMISTRY, v.76, no.3, pp.386 - 393 JOURNAL OF CELLULAR BIOCHEMISTRY 76 3 386 393 scie scopus 000085184500006 2-s2.0-0001471587 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article PROTEIN-COUPLED RECEPTORS MAP KINASE ACTIVATION INDUCED NEURITE RETRACTION TYROSINE-KINASE EGF RECEPTOR MEDIATED ACTIVATION PATHWAY PHOSPHORYLATION BRADYKININ P21(RAS) EGF receptor LPA-signaling G-protein coupled receptor ERK activation neurite retraction PC12 cells