The guanine nucleotide exchange factor ARNO mediates the activation of ARF and phospholipase D by insulin

Hai Sheng Li, Kuntala Shome, Raúl Rojas, Mark A. Rizzo, Chandrasekaran Vasudevan, Eric Fluharty, Lorraine C. Santy, James E. Casanova, Guillermo Romero

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Background: Phospholipase D (PLD) is involved in many signaling pathways. In most systems, the activity of PLD is primarily regulated by the members of the ADP-Ribosylation Factor (ARF) family of GTPases, but the mechanism of activation of PLD and ARF by extracellular signals has not been fully established. Here we tested the hypothesis that ARF-guanine nucleotide exchange factors (ARF-GEFs) of the cytohesin/ARNO family mediate the activation of ARF and PLD by insulin. Results: Wild type ARNO transiently transfected in HIRcB cells was translocated to the plasma membrane in an insulin-dependent manner and promoted the translocation of ARF to the membranes. ARNO mutants: Δ -ARNO and CC-ARNO were partially translocated to the membranes while ΔPH-ARNO and PH-ARNO could not be translocated to the membranes. Sec7 domain mutants of ARNO did not facilitate the ARF translocation. Overexpression of wild type ARNO significantly increased insulin-stimulated PLD activity, and mutations in the Sec7 and PH domains, or deletion of the PH or CC domains inhibited the effects of insulin. Conclusions: Small ARF-GEFs of the cytohesin/ARNO family mediate the activation of ARF and PLD by the insulin receptor.

Original languageEnglish (US)
Article number13
JournalBMC Cell Biology
Volume4
DOIs
StatePublished - Jan 6 2003

All Science Journal Classification (ASJC) codes

  • Cell Biology

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