Role of serine/threonine kinase casein kinase‐II in vascular smooth muscle cell proliferation and inhibition by heparin

Jai Pal Singh, Todd R. Wiernicki, Shalley K. Gupta

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The role of serine/threonine kinase casein kinase‐II (CK‐II) in vascular smooth muscle cell proliferation and inhibition by heparin was investigated. cDNAs for α and β subunits of CK‐II form rabbit vascular smooth muscle cells were cloned and sequenced. A strong evolutionary conservation was found at amino acid and nucleotide levels in CK‐II from rabbit and human. Treatment of smooth muscle cells with a specific antisense oligonucleotide to CK‐II blocked stimulation of DNA synthesis in response to PDGF. Addition of a known inhibitor of CK‐II to cultures of smooth muscle cells also blocked DNA synthesis. Mitogenic stimulation of growth arrested quiescent cultures of smooth muscle cells with PDGF produced a 2–3‐fold increase in CK‐II activity. Heparin was a potent inhibitor of smooth muscle cell derived CK‐II in vitro and attenuated the stimulation of CK‐II activity in response to PDGF in intact cells. Intracellular localization studies showed that heparin and CK‐II were localized in the nucleus. These results suggest a potential role of CK‐II in signal transduction mediating smooth muscle cell growth. Modulation of CK‐II activity by heparin and its co‐localization in the nucleus suggest that heparin may effect CK‐II activity in intact cells. © 1993 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)129-136
Number of pages8
JournalDrug Development Research
Volume29
Issue number2
DOIs
StatePublished - Jun 1993

Keywords

  • casein kinase‐II
  • heparin
  • proliferation
  • smooth muscle cells

ASJC Scopus subject areas

  • Drug Discovery

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