G protein-coupled receptors control vascular smooth muscle cell proliferation via pp60(c-src) and p21(ras)

Bernhard Schieffer, Helmut Drexler, Brian N. Ling, Mario B Marrero

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The binding of vasoactive peptides to their respective G protein- coupled receptors has been implicated in the pathogenesis of vascular smooth muscle cell proliferation, leading to the development of hypertension, arteriosclerosis, and restenosis after vascular injury. We previously showed that the cytosolic tyrosine kinase pp60(c-src) is crucial for angiotensin II (ANG II)-induced activation of the protooncogene p21(ras). Therefore, we investigated the role of pp60(c-src) and p21(ras) in rat aortic smooth muscle cell proliferation induced by several G protein-coupled receptors. ANG II, endothelin-1, or thrombin increased cell proliferation and DNA synthesis. Electroporation of anti-pp60(c-src) antibodies into cells abolished proliferation in response to these G protein-coupled receptor ligands but not in response to platelet-derived growth factor-BB (PDGF-BB). In contrast, electroporation of anti-p21(ras) antibody completely blocked DNA synthesis and cell proliferation in response to ANG II, endothelin-1, thrombin, and PDGF-BB. Our data indicate that the pp60(c-src) tyrosine kinase is necessary and specific for vascular smooth muscle cell proliferation and DNA synthesis in response to G protein-coupled receptors but not classic growth factor receptors.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume272
Issue number6 41-6
StatePublished - Jul 28 1997

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Proto-Oncogene Proteins pp60(c-src)
Proto-Oncogene Proteins p21(ras)
G-Protein-Coupled Receptors
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cell Proliferation
Angiotensin II
Electroporation
Endothelin-1
Thrombin
DNA
Growth Factor Receptors
Antibodies
Arteriosclerosis
Vascular System Injuries
Protein-Tyrosine Kinases
Ligands
Hypertension
Peptides

Keywords

  • Angiotensin II
  • Endothelin-1
  • Platelet-derived growth factor
  • Thrombin
  • Tyrosine kinase

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

G protein-coupled receptors control vascular smooth muscle cell proliferation via pp60(c-src) and p21(ras). / Schieffer, Bernhard; Drexler, Helmut; Ling, Brian N.; Marrero, Mario B.

In: American Journal of Physiology - Cell Physiology, Vol. 272, No. 6 41-6, 28.07.1997.

Research output: Contribution to journalArticle

Schieffer, Bernhard ; Drexler, Helmut ; Ling, Brian N. ; Marrero, Mario B. / G protein-coupled receptors control vascular smooth muscle cell proliferation via pp60(c-src) and p21(ras). In: American Journal of Physiology - Cell Physiology. 1997 ; Vol. 272, No. 6 41-6.
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