Activation of delta-, kappa-, and mu-opioid receptors induces phosphorylation of tuberin in transfected HEK 293 cells and native cells

Eddy H T Wu; Yung H Wong

doi:10.1016/j.bbrc.2005.06.184

Activation of delta-, kappa-, and mu-opioid receptors induces phosphorylation of tuberin in transfected HEK 293 cells and native cells

Biochem Biophys Res Commun. 2005 Sep 2;334(3):838-44. doi: 10.1016/j.bbrc.2005.06.184.

Authors

Eddy H T Wu¹, Yung H Wong

Affiliation

¹ Department of Biochemistry, The Molecular Neuroscience Center, The Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

PMID: 16053916
DOI: 10.1016/j.bbrc.2005.06.184

Abstract

A number of G protein-coupled receptors have been shown to stimulate tuberin phosphorylation, which is critical for the regulation of translation and is apparently involved in neurotrophin-promoted survival of serum-deprived cells. Here, in HEK 293 cells transiently expressing the delta-, kappa-, or mu-opioid receptors, Western blotting analysis using a phosphospecific anti-tuberin antibody revealed a dose- and time-dependent increase in tuberin phosphorylation upon stimulation by specific opioid agonists. In NG108-15, PC12, and SH-SY5Y cells that endogenously express delta-, kappa-, and mu-opioid receptors, respectively, specific opioid agonists also stimulated tuberin phosphorylation in a dose- and time-dependent manner. Pretreatment of cells with pertussis toxin or PI3K inhibitor wortmannin blocked the opioid-stimulated tuberin phosphorylation, implicating the possible involvement of the G(i/o) proteins and the phosphatidylinositol-3 kinase/Akt pathway in opioid-induced tuberin phosphorylation. This is the first study that demonstrates the regulatory role of opioid receptors on tuberin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
Cell Line
Cells, Cultured
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
Enkephalin, D-Penicillamine (2,5)- / pharmacology
ErbB Receptors / metabolism
GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
Humans
Pertussis Toxin / pharmacology
Phosphatidylinositol 3-Kinases / metabolism
Phosphorylation
Receptors, Opioid, delta / physiology*
Receptors, Opioid, kappa / physiology*
Receptors, Opioid, mu / physiology*
Transcriptional Activation
Transfection
Tuberous Sclerosis Complex 2 Protein
Tumor Suppressor Proteins / metabolism*

Substances

Receptors, Opioid, delta
Receptors, Opioid, kappa
Receptors, Opioid, mu
TSC2 protein, human
Tuberous Sclerosis Complex 2 Protein
Tumor Suppressor Proteins
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
Enkephalin, D-Penicillamine (2,5)-
Pertussis Toxin
Phosphatidylinositol 3-Kinases
ErbB Receptors
GTP-Binding Protein alpha Subunits, Gi-Go