Mechanical stretch augments PDGF receptor beta expression and protein tyrosine phosphorylation in pulmonary artery tissue and smooth muscle cells.
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.
Tanabe
Y
Y
Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka-city, Japan.
Saito
M
M
Ueno
A
A
Nakamura
M
M
Takeishi
K
K
Nakayama
K
K
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
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