Peterson T E, Kleppe L S, Caplice N M, Pan S, Mueske C S, Simari R D
Divisions of Cardiovascular Diseases and Biochemistry and Molecular Biology and Molecular Medicine Program, Mayo Clinic and Foundation, Rochester, Minnesota, 55905, USA.
Biochem Biophys Res Commun. 1999 Nov 30;265(3):722-7. doi: 10.1006/bbrc.1999.1738.
Caveolae have been implicated in growth factor receptor and G-protein coupled receptor signaling in vascular cells. It has been postulated that caveolin, the structural protein of caveolae, may act as a general tyrosine kinase inhibitor by binding and inhibiting signaling molecules involved in the activation of the MAP kinase proliferation cascade. Using an in vitro model of VSMC proliferation, we found that serum stimulation caused a dose dependent decrease in both caveolin-1 and caveolin-2 protein levels in human coronary artery smooth muscle cells. Heparin, an inhibitor of VSMC proliferation, inhibited the serum-induced loss of caveolin-1 and caveolin-2. In addition, heparin caused an increase in both caveolin-1 and caveolin-2 localization to caveolae-enriched sucrose gradient membrane fractions when compared to serum alone. Taken together, caveolin may play an important role in the regulation of VSMC proliferation and heparin and serum have opposing effects on caveolin expression and localization in VSMC.
小窝已被证明与血管细胞中的生长因子受体和G蛋白偶联受体信号传导有关。据推测，小窝的结构蛋白小窝蛋白可能通过结合并抑制参与MAP激酶增殖级联激活的信号分子，作为一种通用的酪氨酸激酶抑制剂。使用血管平滑肌细胞增殖的体外模型，我们发现血清刺激导致人冠状动脉平滑肌细胞中小窝蛋白-1和小窝蛋白-2的蛋白水平呈剂量依赖性降低。肝素是血管平滑肌细胞增殖的抑制剂，可抑制血清诱导的小窝蛋白-1和小窝蛋白-2的丢失。此外，与单独使用血清相比，肝素使小窝蛋白-1和小窝蛋白-2在富含小窝的蔗糖梯度膜组分中的定位增加。综上所述，小窝蛋白可能在血管平滑肌细胞增殖的调节中起重要作用，并且肝素和血清对血管平滑肌细胞中小窝蛋白的表达和定位具有相反的影响。
