title: Mechanical stretch augments PDGF receptor beta expression and protein tyrosine phosphorylation in pulmonary artery tissue and smooth muscle cells.
abstract: With regard to the mechanotransduction mechanisms of vasculature involved in hypertensive diseases, we aimed to identify tyrosine-phosphorylated proteins in pulmonary artery that responded to mechanical stress. Mechanical stretch simultaneously augmented protein-tyrosine phosphorylation in p55, p95, p105, p115, p130, p165, p180 in pulmonary artery tissue and pulmonary artery-derived smooth muscle cells (PASMC), whereas p115 and p55 were preferentially phosphorylated by the stretch in endothelial cells (PAEC). A series of experiments designed to characterize these proteins indicated that p115 and p180 were focal adhesion kinase (FAK) and platelet-derived growth factor receptor beta (PDGF-Rbeta), respectively, and that stretch augmented the surface-expression of PDGF-Rbeta in PASMC but not in PAEC. Moreover, a significant increase in the steady-state mRNA level for PDGF-Rbeta was observed in the pulmonary artery of rats with monocrotaline-induced pulmonary hypertension, where the artery should be overstretched due to increasing pulmonary arterial blood pressure. These results suggest that stretch-induced overexpression of cell-surface PDGF-Rbeta as well as augmentation of yrosine phosphorylation of proteins including FAK in PASMC might be involved in the mechanotransduction of pulmonary artery.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka-city, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanabe
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: A
authors.initials: A
authors.lastname: Ueno
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Takeishi
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015139:Blotting, Southern; D015153:Blotting, Western; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D004727:Endothelium / Q000166:cytology; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006976:Hypertension, Pulmonary / Q000139:chemically induced; D008163:Luminescent Measurements; D008297:Male; D016686:Monocrotaline / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis*; D013314:Stress, Mechanical; D013997:Time Factors
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D016686:Monocrotaline; D011505:Protein-Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat