Inhibition of Protein-Tyrosine Kinase Activity in Intact Cells by the Aptameric Action of Oligodeoxynucleotides

Raymond C. Bergan; Edward Kyle; Yvette Connell; Len Neckers

doi:10.1089/ard.1995.5.33

Inhibition of Protein-Tyrosine Kinase Activity in Intact Cells by the Aptameric Action of Oligodeoxynucleotides

Raymond C. Bergan, Edward Kyle, Yvette Connell, Len Neckers

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

Abstract

Direct interaction of oligodeoxynucleotides (ODNs) with proteins represents one of the nonantisense-mediated effects of ODNs. Phosphorothioate-capped ODNs have been shown to inhibit directly the in vitro kinase activity of the chronic myelogenous leukemia-associated protein-tyrosine kinase p210^bcr-abl. In this study we have determined the efficacy of this aptameric ODN in a cellular system using the K562 chronic myelogenous leukemia-derived cell line. Significant effects upon cellular phosphotyrosine content, as well as cellular growth in soft agar, are observed. These effects are sequence specific and are not mediated through changes in p21^bcr-abl protein levels. Additional ODNs are described that also reduce cellular phosphotyrosine levels and inhibit growth in soft agar but do not inhibit p210^bcr-abl kinase activity in vitro.

Original language	English (US)
Pages (from-to)	33-38
Number of pages	6
Journal	Antisense Research and Development
Volume	5
Issue number	1
DOIs	https://doi.org/10.1089/ard.1995.5.33
State	Published - 1995
Externally published	Yes

ASJC Scopus subject areas

Genetics

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10.1089/ard.1995.5.33

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title = "Inhibition of Protein-Tyrosine Kinase Activity in Intact Cells by the Aptameric Action of Oligodeoxynucleotides",

abstract = "Direct interaction of oligodeoxynucleotides (ODNs) with proteins represents one of the nonantisense-mediated effects of ODNs. Phosphorothioate-capped ODNs have been shown to inhibit directly the in vitro kinase activity of the chronic myelogenous leukemia-associated protein-tyrosine kinase p210bcr-abl. In this study we have determined the efficacy of this aptameric ODN in a cellular system using the K562 chronic myelogenous leukemia-derived cell line. Significant effects upon cellular phosphotyrosine content, as well as cellular growth in soft agar, are observed. These effects are sequence specific and are not mediated through changes in p21bcr-abl protein levels. Additional ODNs are described that also reduce cellular phosphotyrosine levels and inhibit growth in soft agar but do not inhibit p210bcr-abl kinase activity in vitro.",

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T1 - Inhibition of Protein-Tyrosine Kinase Activity in Intact Cells by the Aptameric Action of Oligodeoxynucleotides

AU - Bergan, Raymond C.

AU - Kyle, Edward

AU - Connell, Yvette

AU - Neckers, Len

PY - 1995

Y1 - 1995

N2 - Direct interaction of oligodeoxynucleotides (ODNs) with proteins represents one of the nonantisense-mediated effects of ODNs. Phosphorothioate-capped ODNs have been shown to inhibit directly the in vitro kinase activity of the chronic myelogenous leukemia-associated protein-tyrosine kinase p210bcr-abl. In this study we have determined the efficacy of this aptameric ODN in a cellular system using the K562 chronic myelogenous leukemia-derived cell line. Significant effects upon cellular phosphotyrosine content, as well as cellular growth in soft agar, are observed. These effects are sequence specific and are not mediated through changes in p21bcr-abl protein levels. Additional ODNs are described that also reduce cellular phosphotyrosine levels and inhibit growth in soft agar but do not inhibit p210bcr-abl kinase activity in vitro.

AB - Direct interaction of oligodeoxynucleotides (ODNs) with proteins represents one of the nonantisense-mediated effects of ODNs. Phosphorothioate-capped ODNs have been shown to inhibit directly the in vitro kinase activity of the chronic myelogenous leukemia-associated protein-tyrosine kinase p210bcr-abl. In this study we have determined the efficacy of this aptameric ODN in a cellular system using the K562 chronic myelogenous leukemia-derived cell line. Significant effects upon cellular phosphotyrosine content, as well as cellular growth in soft agar, are observed. These effects are sequence specific and are not mediated through changes in p21bcr-abl protein levels. Additional ODNs are described that also reduce cellular phosphotyrosine levels and inhibit growth in soft agar but do not inhibit p210bcr-abl kinase activity in vitro.

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Inhibition of Protein-Tyrosine Kinase Activity in Intact Cells by the Aptameric Action of Oligodeoxynucleotides

Abstract

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