Insulin alters heterogeneous nuclear ribonucleoprotein K protein binding to DNA and RNA

doi:10.1073/pnas.161284098

Insulin alters heterogeneous nuclear ribonucleoprotein K protein binding to DNA and RNA

^*Department of Medicine, University of Washington, Seattle, WA 98195; and ^†Department of Gastroenterology, Medical Center for Postgraduate Education at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland

Communicated by Edwin G. Krebs, University of Washington School of Medicine, Seattle, WA (received for review January 15, 2001)

Abstract

The interaction of the multimodular heterogeneous nuclear ribonucleoprotein (hnRNP) K protein with many of its protein and nucleic acid partners is regulated by extracellular signals. Acting as a docking platform, K protein could link signal-transduction pathways to DNA- and RNA-directed processes such as transcription, mRNA processing, transport, and translation. Treatment of hepatocyte culture with insulin increased K protein tyrosine phosphorylation. Insulin altered K protein interaction with RNA and DNA in vitro. Administration of insulin into mice had similar effects on K protein in liver. Coimmunoprecipitations of RNA with K protein revealed preferential in vivo K protein binding of a subset of transcripts, including the insulin-inducible c-fos mRNA. These results suggest a class of insulin pathways that signal nucleic acid-directed processes that involve K protein.

Footnotes

↵ ‡ To whom reprint requests should be addressed at: Department of Medicine, Box 356521, University of Washington, Seattle, WA 98195. E-mail: karolb{at}u.washington.edu.
Abbreviations:

HTC-IR,

rat hepatoma cells expressing human insulin receptors;

mU,

milliunits;

PI,

phosphatase inhibitor;

IS,

colorimetric immunostaining;

GST,

glutathione S-transferase