EGF family ligand-dependent phenotypic modulation of smooth muscle cells through EGF receptor.
The phenotypic modulation of smooth muscle cells (SMCs) is closely associated with the development and progression of various SMC diseases. We investigated the molecular mechanism of phenotypic modulation triggered by EGF family ligands using a primary culture system of differentiated SMCs. Among four EGF-receptor (EGFR) family members, the EGFR was solely activated by EGF, heparin-binding EGF (HB-EGF), transforming growth factor alpha (TGF alpha), epiregulin (ER), and betacellulin (BTC), resulting in induction of phenotypic modulation of SMCs. This effect was mediated through the coordinated activation of the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) pathways. These results suggest that EGF family ligand- and EGFR-triggered signaling pathways are critically involved in the phenotypic modulation of SMCs.
Yamanaka
Y
Y
Department of Neuroscience (D13), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Hayashi
K
K
Komurasaki
T
T
Morimoto
S
S
Ogihara
T
T
Sobue
K
K
D000818:Animals; D066259:Betacellulin; D002135:Calcium-Binding Proteins / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D002478:Cells, Cultured; D002642:Chick Embryo; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066260:Epiregulin; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010641:Phenotype; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases; D000096985:Calponins
D066259:Betacellulin; D002135:Calcium-Binding Proteins; D002148:Calmodulin-Binding Proteins; D004815:Epidermal Growth Factor; D066260:Epiregulin; D066246:ErbB Receptors; D006133:Growth Substances; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D016211:Transforming Growth Factor alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000096985:Calponins