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Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt.

Publication ,  Journal Article
Kontos, CD; Stauffer, TP; Yang, WP; York, JD; Huang, L; Blanar, MA; Meyer, T; Peters, KG
Published in: Mol Cell Biol
July 1998

Tie2 is an endothelium-specific receptor tyrosine kinase that is required for both normal embryonic vascular development and tumor angiogenesis and is thought to play a role in vascular maintenance. However, the signaling pathways responsible for the function of Tie2 remain unknown. In this report, we demonstrate that the p85 subunit of phosphatidylinositol 3-kinase (PI3-kinase) associates with Tie2 and that this association confers functional lipid kinase activity. Mutation of tyrosine 1101 of Tie2 abrogated p85 association both in vitro and in vivo in yeast. Tie2 was found to activate PI3-kinase in vivo as demonstrated by direct measurement of increases in cellular phosphatidylinositol 3-phosphate and phosphatidylinositol 3, 4-bisphosphate, by plasma membrane translocation of a green fluorescent protein-Akt pleckstrin homology domain fusion protein, and by downstream activation of the Akt kinase. Activation of PI3-kinase was abrogated in these assays by mutation of Y1101 to phenylalanine, consistent with a requirement for this residue for p85 association with Tie2. These results suggest that activation of PI3-kinase and Akt may in part account for Tie2's role in both embryonic vascular development and pathologic angiogenesis, and they are consistent with a role for Tie2 in endothelial cell survival.

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Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

July 1998

Volume

18

Issue

7

Start / End Page

4131 / 4140

Location

United States

Related Subject Headings

  • src Homology Domains
  • Yeasts
  • Vascular Endothelial Growth Factor Receptor-1
  • Tyrosine
  • Recombinant Fusion Proteins
  • Receptor, TIE-2
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
 

Citation

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Kontos, C. D., Stauffer, T. P., Yang, W. P., York, J. D., Huang, L., Blanar, M. A., … Peters, K. G. (1998). Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt. Mol Cell Biol, 18(7), 4131–4140. https://doi.org/10.1128/MCB.18.7.4131
Kontos, C. D., T. P. Stauffer, W. P. Yang, J. D. York, L. Huang, M. A. Blanar, T. Meyer, and K. G. Peters. “Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt.Mol Cell Biol 18, no. 7 (July 1998): 4131–40. https://doi.org/10.1128/MCB.18.7.4131.
Kontos CD, Stauffer TP, Yang WP, York JD, Huang L, Blanar MA, et al. Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt. Mol Cell Biol. 1998 Jul;18(7):4131–40.
Kontos, C. D., et al. “Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt.Mol Cell Biol, vol. 18, no. 7, July 1998, pp. 4131–40. Pubmed, doi:10.1128/MCB.18.7.4131.
Kontos CD, Stauffer TP, Yang WP, York JD, Huang L, Blanar MA, Meyer T, Peters KG. Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt. Mol Cell Biol. 1998 Jul;18(7):4131–4140.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

July 1998

Volume

18

Issue

7

Start / End Page

4131 / 4140

Location

United States

Related Subject Headings

  • src Homology Domains
  • Yeasts
  • Vascular Endothelial Growth Factor Receptor-1
  • Tyrosine
  • Recombinant Fusion Proteins
  • Receptor, TIE-2
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases