Nuclear targeting of FBPase in HL-1 cells is controlled by beta-1 adrenergic receptor-activated Gs protein signaling cascade

Biochim Biophys Acta. 2009 May;1793(5):871-7. doi: 10.1016/j.bbamcr.2009.02.005. Epub 2009 Feb 27.


Muscle fructose 1,6-bisphosphatase (FBPase), a well-known regulatory enzyme of glyconeogenic pathway has recently been found inside nuclei of several cell types (cardiomyocytes, smooth muscle cells, myogenic progenitor cells). This surprising finding raised a question concerning the role of FBPase in this compartment of the cell, and of the extracellular signals regulating nuclear transport of the enzyme. In the present paper we show that, in HL-1 cardiomyocyte cell line, the activity of adenylyl cyclase and cAMP-dependent protein kinase A is essential to nuclear import of FBPase. The import is also stimulated by isoproterenol (a nonselective beta-adrenergic receptors agonist) and inhibited by metoprolol (a selective beta1 antagonist), strongly suggesting that nucleo-cytoplasmic shuttling of FBPase is under the control of beta1-adrenergic receptor-dependent Gs protein signaling cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology*
  • Adenylyl Cyclases / metabolism
  • Adrenergic alpha-Agonists / metabolism
  • Adrenergic beta-Agonists / metabolism
  • Adrenergic beta-Antagonists / metabolism
  • Animals
  • Cell Line
  • Cell Nucleus / enzymology*
  • Colforsin / metabolism
  • Culture Media / chemistry
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Fructose-Bisphosphatase / metabolism*
  • GTP-Binding Protein alpha Subunits, Gs / genetics
  • GTP-Binding Protein alpha Subunits, Gs / metabolism*
  • Isoproterenol / metabolism
  • Metoprolol / metabolism
  • Mice
  • Myocytes, Cardiac* / cytology
  • Myocytes, Cardiac* / metabolism
  • Norepinephrine
  • Receptors, Adrenergic, beta-1 / metabolism*
  • Second Messenger Systems / physiology*


  • Adrenergic alpha-Agonists
  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Culture Media
  • Receptors, Adrenergic, beta-1
  • Colforsin
  • Cyclic AMP-Dependent Protein Kinases
  • Fructose-Bisphosphatase
  • GTP-Binding Protein alpha Subunits, Gs
  • Adenylyl Cyclases
  • Metoprolol
  • Isoproterenol
  • Norepinephrine