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Phosphatidylinositol 3'-kinase and p70s6k Are Required for Insulin but Not Bisperoxovanadium 1,10-phenanthroline (bpV(phen)) Inhibition of Insulin-Like Growth Factor Binding Protein Gene Expression. Evidence for MEK-independent Activation of Mitogen-Activated Protein Kinase by bpV(phen)

Phosphatidylinositol 3'-kinase and p70s6k Are Required for Insulin but Not Bisperoxovanadium 1,10-phenanthroline (bpV(phen)) Inhibition of Insulin-Like Growth Factor Binding Protein Gene Expression. Evidence for MEK-independent Activation of Mitogen-Activated Protein Kinase by bpV(phen)

C J Band, B I Posner

J Biol Chem. 1997 Jan 3;272(1):138-45.

PMID: 8995239

Abstract:

The hormonal regulation of insulin-like growth factor binding protein (IGFBP)-1 and -4 mRNA was compared in serum-free primary rat hepatocyte cultures. The combination of dexamethasone and glucagon (Dex/Gluc) strongly increased IGFBP-1 and IGFBP-4 mRNA levels. Insulin suppressed Dex/Gluc-stimulated IGFBP-1 but not IGFBP-4 mRNA levels. In contrast, the peroxovanadium compound, bisperoxovanadium 1,10-phenanthroline (bpV(phen)), completely abrogated Dex/Gluc induction of both IGFBP mRNA species. Wortmannin and rapamycin blocked the inhibitory effect of insulin but not that of bpV(phen) on Dex/Gluc-stimulated IGFBP mRNA. Thus, although phosphatidylinositol 3'-kinase and p70s6k are necessary for insulin-mediated transcriptional inhibition of the IGFBP-1 gene, a signaling pathway, independent of phosphatidyloinositol 3'-kinase and p70s6k, is activated by bpV(phen) and mediates IGFBP-1 as well as IGFBP-4 mRNA inhibition. Mitogen-activated protein (MAP) kinase activity induced by insulin was suppressed to below basal levels in the presence of Dex/Gluc, whereas in response to bpV(phen), MAP kinase activity was high and unaffected by Dex/Gluc, consistent with a role of MAP kinases in bpV(phen)-mediated inhibition of IGFBP mRNA. The specific MAP kinase kinase (MEK) inhibitor, PD98059, inhibited insulin but not bpV(phen)-stimulated MAP kinase activity, suggesting that MAP kinases can be activated in a MEK-independent fashion. Peroxovanadium compounds are strong inhibitors of tyrosine phosphatases, which may inhibit specific tyrosine/threonine phosphatases involved in the negative regulation of MAP kinases.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP42494735	bpV(phen)		42494-73-5 (anhydrous)	Price

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