PDGF-induced migration of synthetic vascular smooth muscle cells through c-Src-activated L-type Ca²⁺ channels with full-length Ca_V1.2 C-terminus

• Nakada Tsutomu

  Dept. Mol. Pharmacol., Shinshu Univ. Sch. Med. Dept. Inst. Anlys., RCSAS, Shinshu Univ.

• Guo Xiaoguang

  Dept. Mol. Pharmacol., Shinshu Univ. Sch. Med. Dept. Metab. Reg., Shinshu Univ. Sch. Med.

• Kashihara Toshihide

  Dept. Mol. Pharmacol., Shinshu Univ. Sch. Med.

• Aoyama Toshifumi

  Dept. Metab. Reg., Shinshu Univ. Sch. Med.

• Yamada Mitsuhiko

  Dept. Mol. Pharmacol., Shinshu Univ. Sch. Med.

Bibliographic Information

Other Title

• c-Srcによる全長型Ca_V1.2サブユニットを有するL型Ca²⁺チャネルの活性化を介したPDGFによる増殖型血管平滑筋細胞の遊走

Abstract

Platelet-derived growth factor (PDGF) potently induces migration of vascular smooth muscle cells (VSMC); however, molecular mechanism underlying this phenomenon remains unclear. The migration of rat aorta-derived synthetic VSMCs, A7r5, in response to PDGF was potently inhibited by a Ca_V1.2 channel inhibitor, nifedipine, and a Src family tyrosine kinase inhibitor, bosutinib, in a less-than-additive manner. In contractile VSMCs, the C-terminus of Ca_V1.2 is proteolytically cleaved into proximal and distal C-termini (PCT and DCT, respectively). Clipped DCT is noncovalently reassociated with PCT to autoinhibit the channel activity. Conversely, in synthetic A7r5 cells, full-length Ca_V1.2 (Ca_V1.2FL) is expressed much more abundantly than truncated Ca_V1.2. In a heterologous expression system, c-Src was bound to, phosphorylated Tyr1709 and Tyr1758 in PCT and activated Ca_V1.2 channels composed of Ca_V1.2FL significantly more efficiently than Ca_V1.2 (Ca_V1.2delta1763) or Ca_V1.2delta1763 plus clipped DCT. Therefore, in atherosclerotic lesions, phenotypic switching of VSMCs may facilitate pro-migratory effects of PDGF on VSMCs by suppressing posttranslational Ca_V1.2 modifications.

Journal

• Proceedings for Annual Meeting of The Japanese Pharmacological Society

  Proceedings for Annual Meeting of The Japanese Pharmacological Society 92 (0), 2-O-26-, 2019

  Japanese Pharmacological Society

Keywords

• Applied Mathematics
• General Mathematics

Details

• CRID: 1390283659861035520
• NII Article ID: 130007812887
• DOI: 10.1254/jpssuppl.92.0_2-o-26
• ISSN: 24354953
• Web Site: https://www.jstage.jst.go.jp/article/jpssuppl/92/0/92_2-O-26/_pdf
• Text Lang: ja
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed