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Activated α2-macroglobulin binding to cell surface GRP78 induces T-loop phosphorylation of Akt1 by PDK1 in association with Raptor.

Publication ,  Journal Article
Misra, UK; Pizzo, SV
Published in: PLoS One
2014

PDK1 phosphorylates multiple substrates including Akt by PIP3-dependent mechanisms. In this report we provide evidence that in prostate cancer cells stimulated with activated α2-macroglobulin (α2M*) PDK1 phosphorylates Akt in the T-loop at Thr(308) by using Raptor in the mTORC1 complex as a scaffold protein. First we demonstrate that PDK1, Raptor, and mTOR co-immunoprecipitate. Silencing the expression, not only of PDK1, but also Raptor by RNAi nearly abolished Akt phosphorylation at Akt(Thr308) in Raptor-immunoprecipitates of α2M*-stimulated prostate cancer cells. Immunodepleting Raptor or PDK from cell lysates of cells treated with α2M* drastically reduced Akt phosphorylation at Thr(308), which was recovered by adding the supernatant of Raptor- or PDK1-depleted cell lysates, respectively. Studies of insulin binding to its receptor on prostate cancer cells yielded similar results. We thus demonstrate that phosphorylating the T-loop Akt residue Thr(308) by PDK1 requires Raptor of the mTORC1 complex as a platform or scaffold protein.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

2

Start / End Page

e88373

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • Transfection
  • Regulatory-Associated Protein of mTOR
  • RNA, Double-Stranded
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Proto-Oncogene Proteins c-akt
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Phosphothreonine
  • Phosphorylation
 

Citation

APA
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ICMJE
MLA
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Misra, U. K., & Pizzo, S. V. (2014). Activated α2-macroglobulin binding to cell surface GRP78 induces T-loop phosphorylation of Akt1 by PDK1 in association with Raptor. PLoS One, 9(2), e88373. https://doi.org/10.1371/journal.pone.0088373
Misra, Uma Kant, and Salvatore Vincent Pizzo. “Activated α2-macroglobulin binding to cell surface GRP78 induces T-loop phosphorylation of Akt1 by PDK1 in association with Raptor.PLoS One 9, no. 2 (2014): e88373. https://doi.org/10.1371/journal.pone.0088373.
Misra, Uma Kant, and Salvatore Vincent Pizzo. “Activated α2-macroglobulin binding to cell surface GRP78 induces T-loop phosphorylation of Akt1 by PDK1 in association with Raptor.PLoS One, vol. 9, no. 2, 2014, p. e88373. Pubmed, doi:10.1371/journal.pone.0088373.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

2

Start / End Page

e88373

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • Transfection
  • Regulatory-Associated Protein of mTOR
  • RNA, Double-Stranded
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Proto-Oncogene Proteins c-akt
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Phosphothreonine
  • Phosphorylation