TY - JOUR
T1 - Ligand-independent activation of platelet-derived growth factor receptor is a necessary intermediate in lysophosphatidic, acid-stimulated mitogenic activity in L cells
AU - Herrlich, Andreas
AU - Daub, Henrik
AU - Knebel, Axel
AU - Herrlich, Peter
AU - Ullrich, Axel
AU - Schultz, Günter
AU - Gudermann, Thomas
PY - 1998/7/21
Y1 - 1998/7/21
N2 - Growth factor-derived mitogenic signals from the cell surface are transmitted to the nucleus via receptor tyrosine kinases (RTKs), the adaptor proteins Shc and Grb2, and a Ras-dependent protein kinase cascade that activates the extracellular signal regulated kinase (ERK) subfamily of mitogen-activated protein kinases. ERKs also are activated by hormones that stimulate G protein-coupled receptors (GPCRs). We report here that, in agreement with previous data, the epidermal growth factor receptor (EGFR) is a signaling intermediate in ERK activation by GPCRs. Of import, we show that cross-talk between two classes of surface receptors, RTKs and GPCRs, is a general feature. Lysophosphatidic acid not only induces ligand-independent tyrosine autophosphorylation of EGFR but also of platelet-derived growth factor β receptor (PDGF-β-R) as shown by detection of tyrosine phosphorylation and by the use of specific inhibitors of RTKs. The cross- talk appears to be cell type-specific: In L cells that lack EGFR, lysophosphatidic acid-induced Shc and ERK activation is prevented completely by specific inhibition of PDGFR, whereas in COS-7 cells expressing only EGFR, the pathway via EGFR is chosen. In Rat-1 cells, however, that express both EGFR and PDGFR, the EGFR pathway dominates.
AB - Growth factor-derived mitogenic signals from the cell surface are transmitted to the nucleus via receptor tyrosine kinases (RTKs), the adaptor proteins Shc and Grb2, and a Ras-dependent protein kinase cascade that activates the extracellular signal regulated kinase (ERK) subfamily of mitogen-activated protein kinases. ERKs also are activated by hormones that stimulate G protein-coupled receptors (GPCRs). We report here that, in agreement with previous data, the epidermal growth factor receptor (EGFR) is a signaling intermediate in ERK activation by GPCRs. Of import, we show that cross-talk between two classes of surface receptors, RTKs and GPCRs, is a general feature. Lysophosphatidic acid not only induces ligand-independent tyrosine autophosphorylation of EGFR but also of platelet-derived growth factor β receptor (PDGF-β-R) as shown by detection of tyrosine phosphorylation and by the use of specific inhibitors of RTKs. The cross- talk appears to be cell type-specific: In L cells that lack EGFR, lysophosphatidic acid-induced Shc and ERK activation is prevented completely by specific inhibition of PDGFR, whereas in COS-7 cells expressing only EGFR, the pathway via EGFR is chosen. In Rat-1 cells, however, that express both EGFR and PDGFR, the EGFR pathway dominates.
KW - Cross-talk
KW - Epidermal growth factor receptor
KW - G protein-coupled receptors
KW - MAP kinase
UR - http://www.scopus.com/inward/record.url?scp=0032555202&partnerID=8YFLogxK
U2 - 10.1073/pnas.95.15.8985
DO - 10.1073/pnas.95.15.8985
M3 - Article
C2 - 9671791
AN - SCOPUS:0032555202
SN - 0027-8424
VL - 95
SP - 8985
EP - 8990
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 15
ER -