A potential role for nuclear factor of activated T-cells in receptor tyrosine kinase and G-protein-coupled receptor agonist-induced cell proliferation

Chandrahasa R. Yellaturu, Salil K. Ghosh, Radhakrishna Rao, Lisa K. Jennings, Aviv Hassid, Rao Gadiparthi

Research output: Contribution to journalArticle

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Abstract

We have studied the role of nuclear factor of activated T-cells (NFAT) transcription factors in the induction of vascular smooth muscle cell (VSMC) growth by platelet-derived growth factor-BB (PDGF-BB) and thrombin, the receptor tyrosine kinase (RTK) and G-protein-coupled receptor (GPCR) agonists, respectively. NFATc1 but not NFATc2 or NFATc3 was translocated from the cytoplasm to the nucleus upon treatment of VSMCs with PDGF-BB or thrombin. Translocation of NFATc1 was followed by an increase in NFAT-DNA binding activity and NFAT-dependent reporter gene expression. Cyclosporin A (CsA), a potent and specific inhibitor of calcineurin, a calcium/calmodulin-dependent serine phosphatase involved in the dephosphorylation and activation of NFATs, blocked NFAT-DNA binding activity and NFAT-dependent reporter gene expression induced by PDGF-BB and thrombin. CsA also completely inhibited PDGF-BB- and thrombin-induced VSMC growth, as measured by DNA synthesis and cell number. In addition, forced expression of the NFAT-competing peptide VIVIT for calcineurin binding significantly attenuated the DNA synthesis induced by PDGF-BB and thrombin in VSMCs. Together, these findings for the first time demonstrate a role for NFATs in RTK and GPCR agonist-induced growth in VSMCs.

Original languageEnglish (US)
Pages (from-to)183-190
Number of pages8
JournalBiochemical Journal
Volume368
Issue number1
DOIs
StatePublished - Nov 15 2002

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NFATC Transcription Factors
Cell proliferation
G-Protein-Coupled Receptors
T-Cell Antigen Receptor
Protein-Tyrosine Kinases
Cell Proliferation
Thrombin
DNA
Cell growth
Reporter Genes
Vascular Smooth Muscle
Gene expression
Cyclosporine
Smooth Muscle Myocytes
Muscle
Growth
Thrombin Receptors
TCF Transcription Factors
Gene Expression
Calcineurin

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

A potential role for nuclear factor of activated T-cells in receptor tyrosine kinase and G-protein-coupled receptor agonist-induced cell proliferation. / Yellaturu, Chandrahasa R.; Ghosh, Salil K.; Rao, Radhakrishna; Jennings, Lisa K.; Hassid, Aviv; Gadiparthi, Rao.

In: Biochemical Journal, Vol. 368, No. 1, 15.11.2002, p. 183-190.

Research output: Contribution to journalArticle

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