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Nakaike, R., Shimokawa, H., Owada, M.K., Tokunaga, O., Yasutake, H., Kishimoto, T., Imada, C., Shiraishi, T., Egashira, K. and Takeshita, A. (1996) Vanadate Causes Synthesis of Endothelium-Derived NO via Pertussis Toxin-Sensitive G Protein in Pigs. American Journal of Physiology, 271, H296-H302.

has been cited by the following article:

• TITLE: Epidermal Growth Factor Enhances Orthovanadate-Induced Contraction via Src and Myosin Phosphatase Target Subunit 1 in Rat Vascular Smooth Muscle

  AUTHORS: Tomoya Sasahara, Natsumi Ohkura, Mariko Shin, Akira Onodera, Katsutoshi Yayama

  KEYWORDS: Epidermal Growth Factor, Myosin Light Chain Phosphatase, Mitogen-Activated Kinase, Orthovanadate

  JOURNAL NAME: Pharmacology & Pharmacy, Vol.6 No.7, July 29, 2015

  ABSTRACT: Inhibition of protein tyrosine phosphatase by orthovanadate induces vasoconstriction, which is mediated by the Rho kinase-dependent inactivation of myosin light chain phosphatase (MLCP) via signaling downstream of Src-induced activation of the epidermal growth factor (EGF) receptor. The present study investigated the potential role of EGF in orthovanadate (OVA)-dependent vaso-constriction. OVA-induced aortic contraction significantly increased in the presence of EGF, and was abolished by inhibitors of Rho kinase (Y27632), extracellular signal-regulated kinase 1 and 2 (Erk1/2) (FR180204), Erk1/2 kinase (PD98059), EGF receptor (AG1478), and Src (PP2). Treatment of the rat endothelium-denuded thoracic aorta with either EGF or OVA augmented the phosphorylation of myosin phosphatase target subunit 1 (MYPT1) at Thr-853 and of the EGF receptor at Tyr-1173. The phosphorylation of MYPT1 was further increased by co-stimulation with EGF and OVA. EGF receptor phosphorylation at Tyr-845 was also increased by EGF or OVA; this effect was augmented by co-stimulation with EGF and OVA, and was abolished by Src inhibition. In addition, Erk1/2 was phosphorylated by EGF or by co-treatment with EGF and OVA; this was abolished by an EGF receptor inhibitor, but not by Src inhibition. These results suggested that OVA-induced EGF-related contraction was mediated by the Rho kinase-dependent inactivation of MLCP via two different signaling cascades: Src-dependent phosphorylation of the EGF receptor at Tyr-845 and EGF-dependent phosphorylation of Erk1/2.