Platelet-derived Growth Factor-induced H2O2 Production Requires the Activation of Phosphatidylinositol 3-Kinase

Platelet-derived growth factor-induced phosphatidylinositol 3-kinase activation mediates actin rearrangements in fibroblasts.

Various agonist-induced cell responses in neutrophils and fibroblasts, such as chemotaxis and cytoskeletal rearrangements, have been shown to correlate with the synthesis of PtdIns(3,4,5)P3; however, the significance of this rise in second messenger levels is not clear. We show here that wortmannin inhibits platelet-derived growth factor (PDGF)-mediated production of PtdIns(3,4,5)P3 in human fo...

Sequential activation of phosphatidylinositol 3-kinase, beta Pix, Rac1, and Nox1 in growth factor-induced production of H2O2.

The generation of reactive oxygen species (ROS) in cells stimulated with growth factors requires the activation of phosphatidylinositol 3-kinase (PI3K) and the Rac protein. We report here that the COOH-terminal region of Nox1, a protein related to gp91(phox) (Nox2) of phagocytic cells, is constitutively associated with beta Pix, a guanine nucleotide exchange factor for Rac. Both growth factor-i...

Sequential Activation of Phosphatidylinositol 3-Kinase, Pix, Rac1, and Nox1 in Growth Factor-Induced Production of H2O2

Phosphatidylinositol 3-kinase-independent signal transduction pathway for platelet-derived growth factor-induced chemotaxis.

Platelet-derived growth factor (PDGF)-BB is a potent chemoattractant for mesenchymal cells. Intracellular signal transduction for PDGF-induced chemotactic response has been reported to be dependent on phosphatidylinositol 3-kinase (PI3K) activation. Here, we report a PI3K-independent pathway operating for PDGF-induced chemotaxis in vascular smooth muscle cells and other cell types. Two differen...

Stimulation of phosphatidylinositol 3'-kinase association with foca adhesion kinase by platelet-derived growth factor.

We have previously described the stable association of the focal adhesion kinase (FAK) with phosphatidylinositol 3'-kinase (PI3K) in NIH 3T3 cells. This interaction was stimulated by cell adhesion in vivo and by autophosphorylation of recombinant FAK in vitro. In this report, we show that platelet-derived growth factor (PDGF) could also specifically stimulate this association in vivo. This stim...