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β‐Arrestin 2‐mediated heterologous desensitization of IGF‐IR by prolonged exposure of SH‐SY5Y neuroblastoma cells to a mu opioid agonist
Author(s) -
Spartà Antonino,
Baiula Monica,
Campbell Gayle,
Spampinato Santi
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.07.025
Subject(s) - damgo , homologous desensitization , agonist , chemistry , mapk/erk pathway , endocrinology , tyrosine kinase , medicine , phosphorylation , receptor , desensitization (medicine) , microbiology and biotechnology , opioid receptor , biology , biochemistry
Prolonged (12 h) exposure of SH‐SY5Y neuroblastoma cells to the mu‐opioid receptor (MOPr) agonist [D‐Ala 2 ,N‐Me‐Phe 4 ,Gly 5 ‐ol]‐enkephalin (DAMGO) causes homologous desensitization as well as heterologous desensitization of the extracellular signal‐regulated kinase 1/2 (ERK 1/2) phosphorylation induced by insulin‐like growth factor (IGF)‐I. Brief (15 min) but not prolonged exposure to DAMGO transregulates the insulin‐like growth factor‐I (IGF‐I) receptor, as evidenced by its phosphorylation in the absence of IGF‐I. Silencing of β‐arrestin 2 uncouples the crosstalk between the two receptors, thus maintaining IGF‐I‐mediated receptor phosphorylation and ERK 1/2 activation even after prolonged DAMGO exposure. Furthermore, MOPr‐induced activation of IGF‐I receptor requires the tyrosine kinase c‐Src.