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Angiotensin IV enhances phosphorylation of 4EBP1 by multiple signaling events in lung endothelial cells

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Abstract

Angiotensin IV (Ang IV)-stimulated cell proliferation is regulated through activation of multiple signaling modules in lung endothelial cells (EC). Because eukaryotic intitiation factor 4E (eIF4E) binding protein 1 (4EBP1) plays a critical role in the RNA translation and the regulation of cell growth, we examined whether Ang IV modulates expression and/or phosphorylation of eIF4E and 4EBP1 as well as the role of multiple signaling events associated with 4EBP1 phosphorylation in EC. Ang IV stimulation increased phosphorylation but not expression of eIF4E and 4EBP1 proteins. Ang IV stimulation selectively phosphorylated Thr46 > Thr70 > Ser65 but not Thr37 residues in 4EBP1. Pretreatment of cells with PD-98059 and rapamycin, inhibitors of mitogen-activated protein kinase (ERK1/2) and mammalian target for rapamycin (mTOR), respectively, partially blocked Ang IV-mediated phosphorylation of 4EBP1. In contrast, overexpression of p70 ribosomal S6 kinase (p70S6K) and protein kinase B (Akt) enhanced phosphorylation of 4EBP1 and eIF4E binding affinity to the cap region of mRNA. These results support critical roles of multiple signaling and phosphorylation of 4EBP1 by Ang IV in translation process and protein synthesis.

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Authors and Affiliations

  1. Department of Medicine, University of Florida, USA

    Jianghua Lu, Jianalian Zhang, Edward R. Block & Jawaharlal M. Patel

  2. Research Service, VA Medical Center, Gainesville, FL, USA

    Edward R. Block & Jawaharlal M. Patel

  3. Research Service (151), VA Medical Center, 1601 S.W. Archer Road, Gainesville, FL, 32608-1197, USA

    Jawaharlal M. Patel

Authors
  1. Jianghua Lu
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  2. Jianalian Zhang
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  3. Edward R. Block
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  4. Jawaharlal M. Patel
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Correspondence to Jawaharlal M. Patel.

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Lu, J., Zhang, J., Block, E.R. et al. Angiotensin IV enhances phosphorylation of 4EBP1 by multiple signaling events in lung endothelial cells. Mol Cell Biochem 275, 181–188 (2005). https://doi.org/10.1007/s11010-005-1487-8

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  • DOI: https://doi.org/10.1007/s11010-005-1487-8

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