Dynamin inhibits phosphatidylinositol 3-kinase in hematopoietic cells

Duygu Harrison-Findik, Suniti Misra, Suresh K. Jain, Marilyn L. Keeler, Kate A. Powell, Chandra S. Malladi, Lyuba Varticovski, Phillip J. Robinson

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Phosphatidylinositol 3-kinase (PI 3-kinase) plays a role in late stages of endocytosis as well as in cellular proliferation and transformation. The SH3 domain of its regulatory p85 subunit stimulates the GTPase activity of dynamin in vitro. Dynamin is a GTPase enzyme required for endocytosis of activated growth factor receptors. An interaction between these proteins has not been demonstrated in vivo. Here, we report that dynamin associates with PI 3-kinase in hematopoietic cells. We detected both p85 and PI 3-kinase activity in dynamin immune complexes from IL-3-dependent BaF3 cells. However, this association was significantly reduced in BaF3 cells transformed with the BCR/abl oncogene. After transformation only a 4-fold increase in PI 3-kinase activity was detected in dynamin immune complexes, whereas grb2 associated activity was elevated 20-fold. Furthermore, dynamin inhibited the activity of both purified recombinant and immunoprecipitated PI 3-kinase. In BaF3 cells expressing a temperature-sensitive mutant of BCR/abl, a significant decrease in p85 and dynamin association was observed 4 h after the induction of BCR/abl activity. In contrast, in IL-3-stimulated parental BaF3 cells, this association was increased. Our results demonstrate an in vivo association of PI 3-kinase with dynamin and this interaction regulates the activity of PI 3-kinase.

Original languageEnglish (US)
Pages (from-to)10-19
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1538
Issue number1
DOIs
Publication statusPublished - Feb 5 2001

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Keywords

  • Cell signaling
  • Dynamin
  • Endocytosis
  • Hematopoietic cell
  • Phosphatidylinositol 3-kinase
  • Transformation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Harrison-Findik, D., Misra, S., Jain, S. K., Keeler, M. L., Powell, K. A., Malladi, C. S., ... Robinson, P. J. (2001). Dynamin inhibits phosphatidylinositol 3-kinase in hematopoietic cells. Biochimica et Biophysica Acta - Molecular Cell Research, 1538(1), 10-19. https://doi.org/10.1016/S0167-4889(00)00130-0