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 journalArticle

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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

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ADP-Ribosylation Factors
Guanine Nucleotide Exchange Factors
Phospholipase D
Insulin
Membranes
GTP Phosphohydrolases
Insulin Receptor
Cell Membrane
Mutation

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Li, H. S., Shome, K., Rojas, R., Rizzo, M. A., Vasudevan, C., Fluharty, E., ... Romero, G. (2003). The guanine nucleotide exchange factor ARNO mediates the activation of ARF and phospholipase D by insulin. BMC Cell Biology, 4, [13]. https://doi.org/10.1186/1471-2121-4-13
Li, Hai Sheng ; Shome, Kuntala ; Rojas, Raúl ; Rizzo, Mark A. ; Vasudevan, Chandrasekaran ; Fluharty, Eric ; Santy, Lorraine C. ; Casanova, James E. ; Romero, Guillermo. / The guanine nucleotide exchange factor ARNO mediates the activation of ARF and phospholipase D by insulin. In: BMC Cell Biology. 2003 ; Vol. 4.
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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.",
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Li, HS, Shome, K, Rojas, R, Rizzo, MA, Vasudevan, C, Fluharty, E, Santy, LC, Casanova, JE & Romero, G 2003, 'The guanine nucleotide exchange factor ARNO mediates the activation of ARF and phospholipase D by insulin', BMC Cell Biology, vol. 4, 13. https://doi.org/10.1186/1471-2121-4-13

The guanine nucleotide exchange factor ARNO mediates the activation of ARF and phospholipase D by insulin. / Li, Hai Sheng; Shome, Kuntala; Rojas, Raúl; Rizzo, Mark A.; Vasudevan, Chandrasekaran; Fluharty, Eric; Santy, Lorraine C.; Casanova, James E.; Romero, Guillermo.

In: BMC Cell Biology, Vol. 4, 13, 06.01.2003.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The guanine nucleotide exchange factor ARNO mediates the activation of ARF and phospholipase D by insulin

AU - Li, Hai Sheng

AU - Shome, Kuntala

AU - Rojas, Raúl

AU - Rizzo, Mark A.

AU - Vasudevan, Chandrasekaran

AU - Fluharty, Eric

AU - Santy, Lorraine C.

AU - Casanova, James E.

AU - Romero, Guillermo

PY - 2003/1/6

Y1 - 2003/1/6

N2 - 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.

AB - 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.

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