Wortmannin inhibits insulin-induced ras and mitogen-activated protein kinase activation related to adipocyte differentiation in 3T3-L1 fibroblasts

Takashi Uehara, Yukiko Tokumitsu, Yasuyuki Nomura

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29 Citations (Scopus)


Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), inhibited adipocyte differentiation of 3T3-L1 fibroblasts induced by insulin/dexamethasone/IB MX (hormones/IBMX). Insulin as a key factor in the process of the adipocyte differentiation activated PI 3-kinase, Ras protein, and mitogen-activated protein kinase (MAP kinase. ERK) in 3T3-L1 fibroblasts. Pretreatment with wortmannin almost completely suppressed all these activations. These findings suggest that the sequential activation of PI 3-kinase, Ras protein, and MAP kinase is involved in the insulin signaling pathway(s) during differentiation by hormones/IBMX and in consequence of the inhibition of PI 3-kinase by wortmannin, the activation of Ras protein and MAP kinase which acts downstream of PI 3-kinase is suppressed and results in the inhibition of adipocyte differentiation.

Original languageEnglish
Pages (from-to)574-580
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - May 16 1995


ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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