Dynamin inhibits phosphatidylinositol 3-kinase in hematopoietic cells
| Autor: | Phillip J. Robinson, Suniti Misra, Marilyn L. Keeler, Kate A. Powell, Duygu Harrison-Findik, Suresh K. Jain, Chandra S. Malladi, Lyuba Varticovski |
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| Jazyk: | angličtina |
| Předmět: |
Dynamins
Cell signaling GTPase macromolecular substances Endocytosis Cell Line GTP Phosphohydrolases Transformation src Homology Domains Mice Phosphatidylinositol 3-Kinases chemistry.chemical_compound Animals Phosphatidylinositol Enzyme Inhibitors Molecular Biology Cell Line Transformed Phosphoinositide-3 Kinase Inhibitors Dynamin ABL biology Kinase Temperature breakpoint cluster region Hematopoietic cell Cell Biology Hematopoietic Stem Cells Precipitin Tests Molecular biology Guanine Nucleotides Cell biology Enzyme Activation chemistry biology.protein Interleukin-3 GRB2 Mitogens biological phenomena cell phenomena and immunity Phosphatidylinositol 3-kinase |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. (1):10-19 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/S0167-4889(00)00130-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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