Cdc42 Contributes to Phorbol Ester-Induced Ca2+-Independent Contraction of Pulmonary Artery Smooth Muscle

Journal of Veterinary Medical Science

Bokyung KIM¹  SungIl CHO¹  Junghwan KIM¹  Yoon-Jung CHOI¹  Nam-Sik WOO¹  Yoon-Sun KIM¹  Jaeheung KIM¹  Youn Ri LEE¹  Chang-Kwon LEE¹  Won-Ho CHOI¹ 

[1] Department of Physiology and Anesthesiology, College of Medicine, Institute of Biomedical Science and Technology, Konkuk University

关键词: Ca2+-independent contraction;    Cdc42;    protein kinase C;    pulmonary artery smooth muscle;   

DOI  :  10.1292/jvms.67.787

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(35)Cited-By(3)We determined the contribution of the Rho family of low molecular GTP-binding proteins to phorbol ester-induced contraction in swine pulmonary artery smooth muscle. In Ca2+-free medium containing 1 mM EGTA, 12-deoxyphorbol 13-isobutyrate (DPB, 1 μM), a protein kinase C (PKC) activator, elicited sustained contractions, which were not inhibited by treatment with verapamil, a voltage-dependent Ca2+ channel antagonist, and Y27632, a Rho-associated kinase inhibitor. Immunoblot analysis showed three PKC isoforms (α, ε, and ζ) and two Rho GTPases (RhoA and Cdc42) in both cytosolic and the membrane fractions from quiescent strips. DPB (1 μM) significantly induced PKCα and ε to translocate from the cytosolic to the membrane fraction in Ca2+-free medium. DPB also elicited the translocation of Cdc42, but not RhoA to the membrane fraction. Similarly, in the experiment for measurement of Rho GTPase activity by pull-down assay, DPB (1 μM) significantly increased the activity of Cdc42 in Ca2+-free medium. Norepinephrine (NE, 10 μM) stimulated the redistribution of RhoA from the cytosolic to the membrane fraction in swine pulmonary artery smooth muscle. In contrast, NE did not alter the subcellular distributions of Cdc42 and the PKC isoforms. These results indicate that phorbol ester evokes PKC-mediated Ca2+-independent contraction via a Rho GTPase pathway, especially Cdc42, in smooth muscle from swine pulmonary arteries.

【 授权许可】

Unknown