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Insulin inhibits extracellular regulated kinase 1/2 phosphorylation in a phosphatidylinositol 3‐kinase (PI3) kinase‐dependent manner in Neuro2a cells
Author(s) -
Van Der Heide L. P.,
Hoekman M. F.,
Biessels G. J.,
Gispen W. H.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01828.x
Subject(s) - protein kinase b , phosphorylation , kinase , pi3k/akt/mtor pathway , microbiology and biotechnology , phosphatidylinositol , insulin , mapk/erk pathway , biology , protein kinase a , mitogen activated protein kinase kinase , insulin receptor , chemistry , medicine , endocrinology , signal transduction , insulin resistance
Insulin signalling is well studied in peripheral tissue, but not in neuronal tissue. To gain more insight into neuronal insulin signalling we examined protein kinase B (PKB) and extracellular regulated kinase 1 and 2 (ERK1/2) regulation in serum‐deprived Neuro2a cells. Insulin phosphorylated PKB in a dose‐dependent manner but reduced phosphorylation of ERK1/2. Both processes were phosphatidylinositol 3‐kinase (PI3K) dependent. Interestingly, blockade of PI3K in combination with insulin induced phosphorylation of ERK1/2. The phosphorylation of ERK1/2 could be blocked with a specific inhibitor of mitogen‐activated protein/ERK kinase (MEK), suggesting that it was mediated through the highly conserved Ras–Raf–MEK–ERK1/2 pathway. Prolonged exposure to high concentrations of insulin resulted in a desensitized PI3K–PKB route. The insulin‐induced inhibition of ERK1/2 phosphorylation was also diminished when the PI3K–PKB route was desensitized. Blockade of PI3K in combination with insulin, however, still resulted in an unaltered MEK‐dependent phosphorylation of ERK1/2. We conclude that PI3K is an important integrator of insulin signalling in Neuro2a cells as it regulates activation of PKB and inhibition of ERK1/2, and is sensitive to the duration of the insulin stimulus.