Dynamin inhibits phosphatidylinositol 3-kinase in hematopoietic cells

Phosphatidylinositol 3-kinase (PI 3-kinase) plays a role in late stages of endocytosis as well as in cellular proliferation and transformation. The SH 3 domain of its regulatory p85 subunit stimulates the GTPase activity of dy namin in vitro. Dynamin is a GTPase enzyme required for endocytosis of acti vated growth factor receptors. An interaction between these proteins has no t been demonstrated in vivo. Here, we report that dynamin associates with P I 3-kinase in hematopoietic cells. We detected both p85 and PI 3-kinase act ivity in dynamin immune complexes from IL-3-dependent BaF3 cells. However, this association was significantly reduced in BaF3 cells transformed with t he BCR/abl oncogene. After transformation only a 4-fold increase in PI 3-ki nase activity was detected in dynamin immune complexes, whereas grb2 associ ated activity was elevated 20-fold. Furthermore, dynamin inhibited the acti vity of both purified recombinant and immunoprecipitated PI 3-kinase. In Ba F3 cells expressing a temperature-sensitive mutant of BCR/abl, a significan t decrease in p85 and dynamin association was observed 4 h after the induct ion of BCR/abl activity. In contrast, in IL-3-stimulated parental BaF3 cell s, this association was increased. Our results demonstrate an in vivo assoc iation of PI 3-kinase with dynamin and this interaction regulates the activ ity of PI 3-kinase. (C) 2001 Elsevier Science B.V. All rights reserved.